Presence Of Intraductal Carcinoma Research Articles

Detection of intraductal carcinoma in prostate cancer patients with small tumor volume.

The purpose of this study was to investigate intraductal carcinoma of the prostate (intraductal carcinoma) and significant cancer (SC) in patients with small tumor volume (<0.5 cm3 ) in prostatectomy specimens. Data from 639 patients undergoing radical prostatectomy between April 2006 and December 2017 at Chiba University Hospital and 2 affiliated institutions were retrospectively reviewed. Tumor volume in prostatectomy specimens was measured, and with a tumor volume of less than 0.5 cm3 , the presence of intraductal carcinoma and SC was examined. SC was defined as one that did not meet the definition of pathological insignificant cancer (organ-confined cancer, Grade Group 1, tumor volume < 0.5 cm3 ). The number of patients who met four active surveillance (AS) protocols was also examined. A total of 83 patients with tumor volume < 0.5 cm3 were identified in this study population (SC: 43 patients [52%], intraductal carcinoma: 5 patients [6%]). The median follow-up was 34.6 months (range: 18-57 months). Four (5%) developed biochemical recurrence. The number of positive biopsy cores ≥ 2 was an independent predictor of SC in patients with tumor volume < 0.5 cm3 (hazard ratio: 4.39; 95% confidence interval: 1.67-11.56; p = 0.003). In tumor volume < 0.5 cm3 , tumor volume was significantly correlated with the International Society of Urological Pathology Grade Group (1 vs. 4-5, p = 0.002) and the presence of intraductal carcinoma (p = 0.004). In intraductal carcinoma-positive cases, four of five patients (80%) had the predictor of SC, which was two or more positive biopsy cores. Of the four AS protocols, the criteria for Prostate Cancer Research International: Active Surveillance were met most frequently in 46 cases (55%) of tumor volume less than 0.5 cm3 if targeted biopsy by magnetic resonance imaging was available. The results of the present study suggest that intraductal carcinoma was present even in cases with small tumor volumes. Grade Group and intraductal carcinoma showed a positive correlation with tumor volume.

Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs

Within the prostate tumor microenvironment (TME) there are complex multi-faceted and dynamic communication occurring between cancer cells and immune cells. Macrophages are key cells which infiltrate and surround tumor cells and are recognized to significantly contribute to tumor resistance and metastases. Our understanding of their function in the TME is commonly based on in vitro and in vivo models, with limited research to confirm these model observations in human prostates. Macrophage infiltration was evaluated within the TME of human prostates after 72 h culture of fresh biopsies samples in the presence of control or enzalutamide. In addition to immunohistochemistry, an optimized protocol for multi-parametric evaluation of cellular surface markers was developed using flow cytometry. Flow cytometry parameters were compared to clinicopathological features. Immunohistochemistry staining for 19 patients with paired samples suggested enzalutamide increased the expression of CD163 relative to CD68 staining. Techniques to validate these results using flow cytometry of dissociated biopsies after 72 h of culture are described. In a second cohort of patients with Gleason grade group ≥ 3 prostate cancer, global macrophage expression of CD163 was unchanged with enzalutamide treatment. However, exploratory analyses of our results using multi-parametric flow cytometry for multiple immunosuppressive macrophage markers suggest subgroup changes as well as novel associations between circulating biomarkers like the neutrophil to lymphocyte ratio (NLR) and immune cell phenotype composition in the prostate TME. Further, we observed an association between B7–H3 expressing tumor-associated macrophages and the presence of intraductal carcinoma. The use of flow cytometry to evaluate ex vivo cultured prostate biopsies fills an important gap in our ability to understand the immune cell composition of the prostate TME. Our results highlight novel associations for further investigation.

Prognostic value of cribriform size, percentage, and intraductal carcinoma in Gleason score 7 prostate cancer with cribriform Gleason pattern 4

Cribriform Gleason pattern 4 (CGP4) is an indicator of poor prognosis in Gleason Score 7 prostate cancer; however, the significance of the size and percentage of this pattern and the presence of concomitant intraductal carcinoma (IDC) in these patients is unclear. To study the significance of these parameters in radical prostatectomy specimens, 165 cases with CGP4 were identified and reviewed (2017-2019). The size and percentage cribriform pattern and presence of IDC were noted and correlated with adverse pathological features and biochemical recurrence (BCR)-free survival. On review, 156 cases had CGP4 (Grade Group 2: 87 and Grade Group 3: 69). Large cribriform pattern and cribriform percentage of >20% showed significant association with extraprostatic extension, surgical margin positivity, and presence of IDC, whereas the presence of IDC was associated with all the analyzed adverse pathological features. BCR was seen in 22 of 111 (20%) patients after a median follow-up of 11 months, and of these, 21 had large cribriform pattern. On univariate analysis, all parameters had significant predictive values for BCR-free survival except for tertiary Gleason pattern 5. On multivariate analysis, while >20% cribriform pattern was trending to be an independent predictor, only lymphovascular invasion was statistically significant. Large cribriform pattern, >20% cribriform, and presence of IDC are additional pathologic parameters of potential value in identifying patients with high risk for early BCR.

Assessment of MYC/PTEN Status by Gene-Protein Assay in Grade Group 2 Prostate Biopsies

This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non–organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74–24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.

Post-radical prostatectomy (RP) outcome for patients with high-risk prostate cancer treated with intense neoadjuvant hormone therapy (NHT): Results of a pooled analysis of contemporary clinical trials.

238 Background: Patients with high-risk prostate cancer have an increased risk of recurrence and death from prostate cancer. Intense NHT prior to RP has been associated with favorable pathologic responses in a subset of patients with high-risk disease. We conducted a pooled analysis of post-RP outcomes of four, multicenter, randomized, clinical trials of intense NHT prior to RP. Methods: All patients included were enrolled on trials evaluating intense NHT followed by RP. The primary endpoint was time to biochemical recurrence (BCR), defined as the time from RP to prostate specific antigen (PSA) &gt;0.1 ng/mL or start of first post-RP therapy. Secondary endpoints included metastasis-free survival (MFS), overall survival (OS), and time to testosterone recovery. We evaluated outcomes in the overall population, favorable responders (defined as a pathologic complete response or minimum residual disease ≤ 5 mm at RP), and non-responders. We correlated pathologic parameters, including RP pathologic response, PTEN status, ERG status, and presence of intraductal carcinoma with BCR. Results: 121 patients were included of whom 78.5% (n=95) had high-risk disease by NCCN risk categories. Following NHT, 20.7% (n=25) had 0-5 mm of residual tumor (including 9.1%, n=11, with pathologic complete response). Overall, 52 patients (43.0%) experienced BCR, of whom two were exceptional responders (Table). Testosterone recovery was observed in 94.0% of patients (n=109/116). PTEN loss and presence of intraductal carcinoma were associated with shorter time to BCR. Conclusions: In this pooled analysis of clinical trials, we demonstrate that patients who achieve a favorable pathologic response to NHT prior to RP experienced a decreased PSA relapse rate and prolonged time to BCR. Larger residual tumor volumes and tissue-based parameters, including PTEN loss and intraductal carcinoma, were associated with BCR. Additional follow-up is warranted to evaluate the impact on long-term outcomes. Clinical trial information: NCT00298155; NCT00924469; NCT01547299; NCT02268175 . [Table: see text]

Cribriform architecture in radical prostatectomies predicts oncological outcome in Gleason score 8 prostate cancer patients

The Gleason score is an important parameter for clinical outcome in prostate cancer patients. Gleason score 8 is a heterogeneous disease including Gleason score 3 + 5, 4 + 4, and 5 + 3 tumors, and encompasses a broad range of tumor growth patterns. Our objective was to characterize individual growth patterns and identify prognostic parameters in Gleason score 8 prostate cancer patients. We reviewed 1064 radical prostatectomy specimens, recorded individual Gleason 4 and 5 growth patterns as well as presence of intraductal carcinoma, and evaluated biochemical recurrence- and metastasis-free survival. Gleason score 8 disease was identified in 140 (13%) patients, of whom 76 (54%) had Gleason score 3 + 5, 46 (33%) 4 + 4, and 18 (13%) 5 + 3 disease. Invasive cribriform and/or intraductal carcinoma (n = 87, 62%) was observed more frequently in Gleason score 4 + 4 (93%) than 3 + 5 (47%; P < 0.001) and 5 + 3 (44%; P < 0.001) patients. Gleason pattern 5 was present in 110 (79%) men: as single cells and/or cords in 99 (90%) and solid fields in 32 (29%) cases. Solid field pattern 5 coexisted with cribriform architecture (23/32, 72%) more frequently than nonsolid pattern 5 cases (36/78, 46%, P = 0.02). In multivariable analysis including age, prostate-specific antigen, pT-stage, surgical margin status, and lymph node metastases, presence of cribriform architecture was an independent parameter for biochemical recurrence-free (hazard ratio (HR) 2.0, 95% confidence interval (CI) 1.0–3.7; P = 0.04) and metastasis-free (HR 3.5, 95% CI 1.0–12.3; P = 0.05) survival. In conclusion, invasive cribriform and/or intraductal carcinoma occurs more frequently in Gleason score 4 + 4 prostate cancer patients than in Gleason score 3 + 5 and 5 + 3, and is an independent parameter for biochemical recurrence and metastasis. Therefore, cribriform architecture has added value in risk stratification of Gleason score 8 prostate cancer patients.

Practice patterns related to prostate cancer grading: results of a 2019 Genitourinary Pathology Society clinician survey

PurposeTo survey urologic clinicians regarding interpretation of and practice patterns in relation to emerging aspects of prostate cancer grading, including quantification of high-grade disease, cribriform/intraductal carcinoma, and impact of magnetic resonance imaging-targeted needle biopsy. Materials and methodsThe Genitourinary Pathology Society distributed a survey to urology and urologic oncology-focused societies and hospital departments. Eight hundred and thirty four responses were collected and analyzed using descriptive statistics. ResultsEighty percent of survey participants use quantity of Gleason pattern 4 on needle biopsy for clinical decisions, less frequently with higher Grade Groups. Fifty percent interpret “tertiary” grade as a minor/<5% component. Seventy percent of respondents would prefer per core grading as well as a global/overall score per set of biopsies, but 70% would consider highest Gleason score in any single core as the grade for management. Seventy five percent utilize Grade Group terminology in patient discussions. For 45%, cribriform pattern would affect management, while for 70% the presence of intraductal carcinoma would preclude active surveillance. ConclusionThis survey of practice patterns in relationship to prostate cancer grading highlights similarities and differences between contemporary pathology reporting and its clinical application. As utilization of Gleason pattern 4 quantification, minor tertiary pattern, cribriform/intraductal carcinoma, and the incorporation of magnetic resonance imaging-based strategies evolve, these findings may serve as a basis for more nuanced communication and guide research efforts involving pathologists and clinicians.

Abstract 3620: Histopathological associations with PTEN and ERG status in prostate biopsies from men treated with radiation

Abstract Loss of the PTEN tumor suppressor gene in prostate cancer, which usually occurs by genomic deletion, is associated with adverse outcome. Recent work (PMID:23888040) suggested that PTEN activity is also required for maintaining genomic integrity and its loss may be associated with resistance to DNA damaging agents, such as ionizing radiation. We assembled a series of patients with intermediate to high grade clinically localized prostate cancer who underwent external beam radiation as their primary treatment. We obtained and regraded all positive biopsy cores according the the new Grade Grouping system for Gleason scores (PMID: 26492179) and performed analytically and clinically validated IHC assays for PTEN (associated with PTEN genomic alterations) and ERG (associated with the TMPRSS2-ERG gene fusion) on all positive tissue cores from a given biopsy that were contained in up to 5 separate FFPE blocks (n=589 positive cores, n positive cores ranged from 1 to 13, with median of 2 and mean of 3) from 193 patients. PTEN and ERG status were correlated with the new Grade Groups as well as other histopathological features, including the presence of cribriform architecture and intraductal carcinoma. Patients were 66% White, and 27% African American, and median age was 68.5. Grade Group designations (taken as the highest Grade group in the case) were as follows (Group 1 = 27%, Group 2 = 30%, Group 3= 15%, Group 4 = 18%, Group 5 = 11%). Overall there was at least some PTEN loss in 36% of cases. The presence of any PTEN loss in a given case was strongly associated with Grade Group (P&amp;lt;0.001, chi square), in that 17% of patients with Grade Group 1 showed any PTEN loss and 77% of patients with Grade Group 5 showed any PTEN loss. As seen in prior studies, PTEN loss was frequently heterogeneous in that only 11% of cases overall showed complete loss of PTEN in all tumor tissue examined. Homogeneous PTEN loss was also significantly associated with Grade Groups since 3.8% of cases of Grade Group 1 showed such loss and 27% of cases of Grade Group 5 showed such loss (P=0.024, chi square). PTEN loss was also associated with cribriform morphology (P&amp;lt;0.001) and the presence of intraductal carcinoma of the prostate (P&amp;lt;0.001), both known independent prognostic factors. Having any PTEN loss was also associated with ERG gene fusions since 22% of cases showed PTEN loss that were negative for ERG and 52% of cases showed PTEN loss in cases positive for ERG (P&amp;lt;0.000). As also previously found, the rate of PTEN loss was higher in samples from White patients than African Americans (complete PTEN loss = 3.9% in African Americans and 14% in White patients). The presence of any ERG positive tumor was also higher in tissues from White patients (54%) compared to African Americans (29%) (P=0.003). Additional analyses are underway regarding associations between PTEN and ERG status and outcomes after radiation therapy. Citation Format: Onur Ertunc, Mark Markowski, Phuoc T. Tran, Amol Narang, Jessica Hicks, Daniel Song, Jiayun Lu, Elizabeth A. Platz, Theodore Deweese, Angelo M. De Marzo. Histopathological associations with PTEN and ERG status in prostate biopsies from men treated with radiation [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 3620.

Abstract NG06: The clinico-genomics of localized, non-indolent prostate cancer: the CPC-GENE experience

Abstract NG06: The clinico-genomics of localized, non-indolent prostate cancer: the CPC-GENE experience

Quantitative perineural invasion is a prognostic marker in prostate cancer

This study aimed to investigate the prognostic value of a quantitative, detailed, yet practical analysis of perineural invasion in radical prostatectomy specimens in a high-risk prostate cancer cohort. A total of 114 patients with prostate cancer who underwent radical prostatectomy between 2000 and 2013 were analysed. Using S100 protein immunohistochemistry assisted in the detection of nerves. In the area of closest proximity of the tumour to the dorso-lateral margins, nerves were counted and the infiltration of nerves was categorised (0-3). Category 0 was nerves without immediate tumour-cell-contact. All nerves being fully surrounded by tumour (classical perineural carcinosis) were categorised group 3. Two further categories discriminated between nerves that were touched either by carcinoma cells below 50% of the circumference (category 1) or above (category 2). Perineural carcinosis (Pn1) was seen in 61.4% of cases and correlated positively with ISUP grades, pT categories and presence of intraductal carcinoma but failed significance on Kaplan-Meier analysis. A more quantitative analysis of percentual perineural involvement did demonstrate significant survival differences: cases with less than one Pn1-positive nerve in 5 high power fields had longer survival times. Incomplete perineural involvement (category 1-2) did not have a prognostic value, endorsing the current definition of perineural carcinosis as full circumferential encasement of a nerve by tumour cells. A quantitative analysis of the percentage of nerves positive for perineural invasion has a higher prognostic value than the classical dichotomous statement on the mere presence of perineural invasion.

Abstract 4339: Prognostic significance of copy number alteration burden in unfavorable intermediate-risk prostate cancers harboring intraductal carcinoma and cribriform architecture

Abstract Aim: Men with intermediate-risk prostate cancer represent a heterogeneous group of patients with varying prognoses. Intraductal carcinoma (IDC), cribriform architecture (CA), and high copy number alteration burden are novel pathological and genomic indices that predict aggressive disease and inferior clinical outcomes in patients with localised prostate cancer. We aimed to test the independent prognostic effect of these indices in a cohort of intermediate-risk prostate cancers. Experimental methods: We defined a set of clinical and genomic indices to test for their prognostic significance in a cohort of individuals with NCCN-defined intermediate-risk prostate cancer, who were treated with radical prostatectomy (RadP) or radiotherapy (RT) (N = 173, RadP; N = 358, RT). Clinical indices include primary T-category, pre-treatment PSA level, Gleason's score and pattern, and presence of IDC and/or CA. Pathological features were reviewed centrally by two expert pathologists. Copy number alteration burden was assessed in 215 tumours of the cohort using SNP array profiling (Affymetrix Oncoscan), and reported as percent genome aberration (PGA). Our primary endpoint was to test if a model incorporating IDC/CA and PGA stratifies patients with intermediate-risk disease for risk of biochemical relapse after primary treatment. Results: Biochemical relapse was associated with PGA on univariable and multivariable analysis for the sub-cohort of 215 patients (HR of High vs Low PGA defined by median = 1.61, 95% CI = 1.04-2.49, Wald's p = 0.033). Based on modelling of the clinical indices, presence of IDC/CA was associated with biochemical relapse-free rate (bRFR) on univariable and multivariable analyses (HR = 1.90, 95% CI = 1.34-2.69, p = 0.00034), along with PSA level. Risk stratification considering both IDC/CA and PGA indicated an additive prognostic effect of IDC/CA to PGA for early biochemical relapse, with 18-month bRFR of 83% in High PGA, present IDC/CA vs 94% in Low PGA, absent IDC/CA subgroups (HR = 2.55, 95% CI = 1.49-4.39, p = 0.00069). A comparison of risk stratification models revealed that inclusion of PGA to IDC/CA yielded the strongest model for predicting 18-month bRFR in patients with intermediate-risk prostate cancer following treatment (area under the curve, AUC = 0.580, 95% CI = 0.456-0.675 [T-category, PSA, and IDC/CA] vs 0.649, 95% CI = 0.476-0.776 [T-category, PSA, IDC/CA, and PGA]). Conclusions: We herein demonstrate for the first time a novel risk stratification model integrating pathological (IDC/CA) and genomic (PGA) indices to identify patients with unfavourable intermediate-risk prostate cancer, who may benefit from intensification to conventional definitive treatment. Citation Format: Melvin Lee Kiang Chua, Jure Murgic, Melania Pintilie, Emilie Lalonde, Charlotte Kweldam, Winnie Lo, Alejandro Berlin, Alan Dal Pra, Michele Orain, Valerie Picard, Helene Hovington, Alain Begeron, Yves Fradet, Bernard Tetu, Julie Livingstone, Alice Meng, Jun Yan Zhang, Gaetano Zafarana, Neil Fleshner, Mike Fraser, Paul Boutros, Robert Bristow, Theodorus van der Kwast. Prognostic significance of copy number alteration burden in unfavorable intermediate-risk prostate cancers harboring intraductal carcinoma and cribriform architecture. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4339.

A Novel System for Estimating Residual Disease and Pathologic Response to Neoadjuvant Treatment of Prostate Cancer.

Pathologic variables that characterize response of prostate carcinoma to current neoadjuvant therapy have not been characterized in detail. This study reports (i) the histological features of prostate cancer treated with abiraterone and enzalutamide and inter-pathologist variance in identifying these features, and (ii) the effect of the novel androgen deprivation agents on residual cancer volume. We reviewed sections of prostatectomies from 37 patients treated with neoadjuvant agents and 22 untreated patients, tabulated the frequency of nine features of cancer (intact cancer glands, isolated cancer cells, poorly formed glands, cribriform architecture, clear spaces, intraductal carcinoma, solid sheets of cancer cells, prominent nucleoli, and previously described ABC grouping) and two features of benign glands (prominent basal cells and coalescent corpora amylacea). We used several methods, including a novel metric (visual grid system), to estimate residual tumor volume. The most highly reproducible features were ABC grouping (κ = 0.56-0.7), presence of intraductal carcinoma (κ = 0.34-0.72), cribriform architecture (κ = 0.42-0.68), solid sheets of tumor cells (κ = 0.44-0.56), and coalescent corpora amylacea (κ = 0.4-0.54). Among poorly reproducible features were prominent nucleoli (κ = 0.03-0.11), clear spaces (κ = 0.05-0.07), and poorly formed cancer glands (κ = 0.02-0.1). Determination of tumor mass was excellent regardless of the method used-maximum tumor size (κ = 0.9-0.94), tumor area (κ = 0.94-0.96), and grid-based tumor cellularity (κ = 0.9). We propose using a set of parameters including maximum tumor size, tumor area/volume, cellularity, volume, and ABC grouping for evaluating radical prostatectomies post-neoadjuvant therapy. Prostate 76:1285-1292, 2016. © 2016 Wiley Periodicals, Inc.

Effect of androgen deprivation therapy on intraductal carcinoma of the prostate (IDC-P), a prognostic factor for prostate cancer.

146 Background: The presence of intraductal carcinoma of the prostate (IDC-P) is reported to be an adverse prognostic factor for cancer-specific survival (CSS) in localized and metastatic prostate cancer patients. However, there is no data indicating whether the presence of IDC-P can be affected by ADT (androgen deprivation therapy). Methods: We retrospectively evaluated 152 high risk prostate cancer patients who underwent radical prostatectomy with neoadjuvant ADT. They were diagnosed and treated at author-affiliated hospitals between 1991 and 2005. All patient data was made available from slides prepared from prostate needle biopsy samples and prostatectomy specimens and each patient received ADT before operation. Slides were re-reviewed by a single genitourinary pathologist (T.T.) according to the 2005 International Society of Urological Pathology (ISUP) grading system and presence of IDC-P was defined using previously published diagnostic criteria. Results: Patient median age was 68 years (range 46-80 years). The median iPSA was 32.7 ng/ml (range 2.4-296). The median follow-up period was 109 months (range 11-257). Sixty-one patients (40%) were ≥cT3 and 113 cases (74%) had biopsy Gleason score ≥8. Preoperative median ADT period was 4 months (range 1–20 ). IDC-P component was detected in 54 patients (36%) in needle biopsy and 69 (45%) in prostatectomy. There were 28 patients who died of the disease and 12 patients who died of other causes during follow-up. They were divided in 4 groups according to with or without IDC-P in biopsy/prostatectomy (-/- 68cases ,-/+ 30, +/- 15, +/+ 39). Twenty eight per cent of IDC-P positive cases in biopsy showed disappearance of IDC-P in prostatectomy specimen. Prognosis was the worst in +/+ group and IDC-P disappearance cases (+/-) tended to have better survival than IDC-P existing cases (+/+) in CSS (p = 0.04). Conclusions: In a number of IDC-P-positive cases determined by needle biopsy, the disappearance of IDC-P in prostatectomy specimens after ADT indicates the possibility that part of IDC-P positive patients can occasionally respond to ADT.

Not all gleason pattern 4 prostate cancers are created equal: A study of latent prostatic carcinomas in a cystoprostatectomy and autopsy series.

The Gleason grading system represents the cornerstone of the management of prostate cancer. Gleason grade 4 (G4) is a heterogeneous set of architectural patterns, each of which may reflect a distinct prognostic value. We determined the prevalence of the various G4 architectural patterns and intraductal carcinoma (IDC) in latent prostate cancer in contemporary Russian (n = 220) and Japanese (n = 100) autopsy prostates and in cystoprostatectomy (CP) specimens (n = 248) collected in Italy. We studied the association of each G4 pattern with extraprostatic extension (EPE) and tumor volume to gain insight into their natural history. Presence of IDC and nine architectural features of Gleason grade 4 and 5 cancer were recorded. The prevalence of Gleason score ≥ 7 PC was higher in the autopsy series (11%) compared to the CP series (6.5%, P = 0.04). The prevalence of IDC and carcinoma with a cribriform architecture was 2.2% and 3.4% in the autopsy series and 0.8% and 3.6% in the cystoprostatectomy series, respectively. In multivariable analysis, cribriform architecture was significantly associated with increased tumor volume (P < 0.001) and EPE (OR:11.48, 95%CI:2.30-57.16, P = 0.003). IDC was also significantly associated with EPE (OR:10.08, 95%CI:1.58-64.28, P = 0.014). Small fused glands had a strong negative association with EPE in the autopsy series (OR:0.06, 95%CI:0.01-0.58, P = 0.015). Our study revealed that in latent prostate cancer both cribriform architecture and IDC are uniquely associated with poor pathological outcome features. In contrast, Gleason score 7 (3 + 4) cancers with small-fused gland pattern might possibly include some prostate cancers with a more indolent biology.

118 The presence of intraductal carcinoma of the prostate in needle biopsy is a significant prognostic parameter for prostate cancer patients with distant metastasis

118 The presence of intraductal carcinoma of the prostate in needle biopsy is a significant prognostic parameter for prostate cancer patients with distant metastasis

The presence of intraductal carcinoma of the prostate in needle biopsy as a prognostic parameter for prostate cancer patients with distant metastasis.

237 Background: The presence of intraductal carcinoma of the prostate (IDC-P) is an adverse prognostic factor for prostate-specific antigen (PSA) failure, progression-free survival, and cancer-specific survival (CSS) in localized prostate cancer patients. However, there is no data indicating whether the presence of IDC-P can influence outcome in prostate cancer patients with distant metastasis at presentation. We aimed to evaluate whether IDC-P in needle biopsies is also an adverse prognostic parameter for CSS in prostate cancer patients with distant metastasis. Methods: We retrospectively evaluated 159 prostate cancer patients with distant metastasis who presented at the hospitals that the authors are affiliated with between 2002 and 2012 and reviewed the slides prepared from prostate needle biopsy specimens. Data on the patient age, performance status, clinical T stage, serum PSA, C-reactive protein, alkaline phosphatase (ALP), hemoglobin (Hb), albumin, serum calcium, biopsy Gleason score (&gt; 8 or not), the presence of Gleason pattern 5, the percent of the core involved with cancer, and the maximum percent of a core involved with cancer were analyzed. Patient characteristics were analyzed using the Fisher's exact test. Multivariate Cox proportional hazard regression models were developed to predict CSS. Results: Patient median age was 73 years (range 47–90 years). The median serum PSA was 290 ng/mL (range 4.18–10,992 ng/mL). The median follow-up period was 36 months (range 3–120 months). IDC-P component was detected in 103 (64.8%) patients. There were 82 patients who died of the disease and 6 patients who died of other causes. Using univariate analysis, IDC-P (p = 0.0001), the presence of Gleason pattern 5 (p = 0.005), the percent of the core involved with cancer (p = 0.002), Hb (p = 0.001), and high ALP (p = 0.002) were all shown to be significantly associated with CSS. In the multivariate analysis, only IDC-P (p = 0.016; hazard ratio, 2.187) was significantly associated with CSS. Conclusions: The presence of IDC-P in needle biopsy is a prognostic parameter for CSS in patients with distant metastasis at presentation.

ERG positive prostatic cancer may show a more angiogenetic phenotype

In Western populations, roughly half of prostatic carcinoma (PC) cases show translocations involving the ETS transcription factor family genes and overexpression of the ERG transcription factor. ETS transcription factor family is known to be involved in angiogenesis. Microvascular density (MVD) influences the prognosis of various solid tumors, yet its significance in PC remains unclear. The aim of the study was to analyze microvascular density in prostatic adenocarcinoma in relationship to ERG expression. This is a retrospective study of 112 cases whose aim is to compare MVD in ERG-positive and negative cases and to test its relationship with other pathological parameters. Immunohistochemical stains for ERG and CD31 were done using standard methods, using tissue microarrays. The cases were classified as ERG-positive and negative and the CD31-positive vessels were counted. Fifty-one cases (45.54%) were positive for ERG, and the average MVD was 111.81vessels/mm2 (standard deviation, SD 54.20) for the entire group, 101.30vessels/mm2 (SD 50.60) for ERG-negative and 124.38vessels/mm2 (SD 56.17) for ERG-positive cases. There was only a slight tendency for higher MVD in higher grades and stages of cancer. None of other parameters, such as patients’ age, lymphovascular invasion, presence of intraductal carcinoma or positive surgical margin, showed a significant relationship to MVD. This shows for the first time that ERG expression and MVD may have a significant relationship in prostatic adenocarcinoma.

Presence of intraductal carcinoma of the prostate on needle biopsy as a prognostic factor for prostate cancer in radical prostatectomy patients.

268 Background: Intraductal carcinoma of the prostate (IDCP) is seen with widely invasive, biologically aggressive prostate cancer. A recent study has shown this morphologic pattern is useful for prognostication of biochemical recurrence after radical prostatectomy, whereas there is no paper to report biopsy finding of IDCP to be a positive predictor of progression-free survival (PFS) and cancer-specific survival (CSS). Methods: This retrospective study included men with high-risk prostate cancer treated with radical prostatectomy between 1991 and 2005, and we reviewed slides of biopsy samples. Presence of IDCP was defined using previously published diagnostic criteria by a single genitourinary pathologist. Analyzed factors included age, prostate-specific antigen (PSA), clinical T stage, higher biopsy Gleason score (bGS), presence of Gleason pattern five, and IDCP on biopsy samples. Finally, a total of 205 patients with high-risk prostate cancer were entered in our retrospective clinicopathological analysis. Results: Patient mean age was 68. Baseline characteristics included a PSA greater than 20 ng/ml at diagnosis in 122 cases (60%), clinical stage greater than T2 (cT) in 86 (42%), and bGS ³a8 in 150 (73%) in all patients. Follow-up period was 86 months on average. The presence of IDCP on needle biopsy was in 75 (37%). Forty-four patients showed clinical failure, and 20 patients died of the disease. Patients with IDCP showed a higher increased PSA level, higher increased bGS, and more advanced cT than those without IDCP (p &lt; 0.0001). In univariate analysis, IDCP (p &lt; 0.0001), cT (p &lt; 0.0001), bGS (p = 0.0002), and presence of Gleason pattern five (p=0.004) were significantly associated with PFS; IDCP (p &lt; 0.001) and cT (p = 0.02) were significantly associated with CSS. In multivariate analysis, IDCP (p&lt; 0.0001; hazard ratio (HR), 3.574) and cT (p= 0.004; HR, 3.087) were significantly associated with PFS; IDCP (p = 0.001; HR, 8.405) and PSA level (p = 0.0044; HR, 2.920) were significantly associated with CSS. Conclusions: Presence of IDCP on needle biopsy can be a significant predictor of PFS and CSS when analyzing factors of biopsy samples in high risk prostate cancer.

713 Presence of intraductal carcinoma of the prostate on needle biopsy can be a significant prognostic factor

713 Presence of intraductal carcinoma of the prostate on needle biopsy can be a significant prognostic factor

Predictors of early relapse in high risk prostate cancer patients treated with neoadjuvant mitoxantrone and docetaxel

4640 Background: The addition of chemotherapy (CTX) to primary treatment is being evaluated in clinical trials to improve outcomes in high-risk prostate cancer. Factors that predict relapse after combined treatment with CTX and radical prostatectomy (RP) are not known. Understanding which clinical and pathologic factors affect outcome can facilitate the design of studies of combined modality treatment of high-risk prostate cancer. Methods: Using the Kaplan-Meier method and log-rank test for univariate analyses and Cox’s proportional hazards regression for the multivariate analysis, we examined the relationship between progression-free survival (PFS, defined as time to serum PSA ≥ 0.4 ng/mL) and a series of variables in men with high risk prostate cancer (cT2b or T3a or PSA ≥ 15 ng/mL or Gleason score (GS) ≥ 4+3) who received 4 cycles of docetaxel (35 mg/m2) and mitoxantrone (2–5 mg/m2) weekly for 3 of every 4 weeks prior to RP. Pre-CTX variables were PSA, PSA density (PSAD), age, biopsy GS, and cT stage. Post-treatment variables were: CTX doses delivered, %PSA change, surgical GS, pT stage, pN stage, margin status, Ki-67 index (% Ki-67 staining cells/total cancer cells from a tissue microarray), and presence of intraductal carcinoma (IDC). Results: 48 patients received at least 1 cycle of CTX and were evaluable for efficacy endpoints. Median follow-up is 18.6 months. Estimated PFS at 2 years is 70±14%. In univariate analyses PSA ≥ 15 ng/dL (p=0.02), presence of IDC (p=0.003), and lymph node metastases (+LN) (p<0.001) were associated with shorter PFS. In a multivariate analysis of pre-treatment factors, PSAD (HR 1.25 per 0.1 ng/ml/cc, 95%CI 1.03–1.5, p=0.03) was the only factor significantly associated with shorter PFS. When both pre- and post-treatment factors were included, PSAD (HR 1.3 per 0.1 ng/ml/cc, 95%CI 1.05–1.6, p=0.02) and +LN (HR 27, 95% CI 6–125, p<0.001) were independent predictors of shorter PFS. There was a trend for biopsy GS 8–10 (HR 3.9, 95%CI 0.9–16.9, p=0.068). Conclusions: Our early results show that in high risk prostate cancer treated with neoadjuvant chemotherapy followed by radical prostatectomy, PSAD and persistent nodal disease are significantly associated with early relapse. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, OSI