Presence Of Intraductal Carcinoma Of The Prostate Research Articles

The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy

ObjectiveTo explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer. MethodsEighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology. ResultsIDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176–10.971, P = 0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234–11.930, P = 0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis. ConclusionIDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.

Predictor of adverse pathology in patients who underwent deferred radical prostatectomy following active surveillance: Results from multi-institutional prospective observational cohort in the PRIAS-JAPAN.

350 Background: Intraductal carcinoma of the prostate (IDC-P) and invasive cribriform are key prognostic pathologies among early stage prostate cancer patients; however, predictors of adverse pathology, including these types, remain unknown. In men who opted for active surveillance (AS), we aimed to examine the association between adverse pathology and patient characteristics, utilizing radical prostatectomy (RP) specimens. Methods: We re-reviewed available RP specimens from 1035 men prospectively enrolled in the PRIAS-JAPAN cohort between January 2010 and September 2020. We defined adverse pathology on RP specimen as Gleason grade group of ≥3, pT-stage≥T3, pN positivity, or the presence of IDC-P or invasive cribriform. And, we examined the predictive factors associated with adverse pathology, using factors at AS enrollment and before RP. Results: Out of 162 men underwent RP, available 137 RP specimens were analyzed. The percentage of adverse pathology was 48.9% (67 patients), including 8.8% in IDC-P and 29.9 % in invasive cribriform. Men with adverse pathology had lower prostate specific antigen recurrence-free survival than those without them (log rank P = 0.0189). On multivariate logistic regression analyses, increasing age at AS enrollment and before RP were the predictive factors for adverse pathology (Odds ratio [OR], 1.1; 95% confidence interval [CI]: 1.02-1.19, P = 0.0178, OR, 1.12; 95% CI: 1.02-1.22, P=0.0126), not magnetic resonance imaging findings. Conclusions: Aging is significantly associated with adverse pathology including IDC-P or cribriform. The results suggest that relaxing scheduled examinations during AS depending on age is not practical. Clinical trial information: UMIN000048095 .

Cribriform pattern and intraductal carcinoma of the prostate can have a clinicopathological impact, regardless of their percentage and/or number of cores

Cribriform pattern and intraductal carcinoma of the prostate (IDC-P) are widely accepted as poor prognostic factors in prostate cancer. However, it remains unclear to what extent the presence of these morphological features in prostate biopsy specimens, as diagnosed by hematoxylin-eosin-stained specimens only, affects the clinicopathological impact. In this study, we summarized the characteristics of the cribriform pattern and IDC-P in 850 prostate biopsy cases. The results showed a statistically significant increase in the incidence of cribriform pattern and IDC-P as grade group (GG) increased (especially in cases ≥ GG4, Chi-square test P<0.001). The independent risk factors for cribriform pattern and IDC-P in biopsy specimens in the multivariate logistic regression analysis were the former GG, presence of IDC-P, lesion length of the highest GG core, latter GG, presence of the cribriform pattern, number of biopsies obtained, and number of highest GG core. Overall, 125 cases in which radical prostatectomy was conducted after biopsy were selected for further analysis. Multivariate logistic regression analysis using biopsy and surgical specimens confirmed that the presence of the cribriform pattern and IDC-P in biopsy specimens were independent risk factors for lymph node metastasis (odds ratios [95% confidence interval] were 6.54 [1.15‒37.05] for the cribriform pattern and 23.71 [1.74‒322.42] for IDC-P). The presence of the cribriform pattern and/or IDC-P in a biopsy specimen was a significant factor, even if only partially present, indicating lymph node metastasis. However, further validation is required to predict poor prognostic factors more accurately.

Abstract No. 110 Intraductal carcinoma of the prostate in the era of mpMRI-targeted prostate biopsies: clinical, pathologic and radiologic characteristics

Since 2018, there is increasing adoption of mpMRI to detect prostate cancer, particularly in the pre-biopsy setting. Recent studies showed that mpMRI is a sensitive tool for detecting cancers harboring intraductal carcinoma of the prostate (IDC-P). The presence of IDC-P has been associated with adverse pathological features and worse clinical outcomes. The goals of this study were to 1) determine frequency of IDC-P detected on biopsy in the mpMRI era and 2) assess the MRI and pathologic characteristics of biopsy proven IDC-P.

Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2–ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate–ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor.

The heterogeneity of intraductal carcinoma of the prostate is associated with different efficacy of standard first-line therapy for patients with metastatic castration-resistant prostate cancer.

BackgroundTo explore whether metastatic castration‐resistant prostate cancer (mCRPC) patients with distinct intraductal carcinoma of the prostate (IDC‐P) subtypes respond differently to abiraterone and docetaxel treatment.MethodsWe retrospectively analyzed data of 170 mCRPC patients receiving abiraterone or docetaxel as first‐line therapy. PSA response, PSA progression‐free survival (PSA‐PFS), radiographic progression‐free survival (rPFS), and overall survival (OS) were analyzed based on the presence of IDC‐P and its subpatterns.ResultsIDC‐P was confirmed in 91/170 (53.5%) patients. Among them 36/91 (39.6%) and 55/91 (60.4%) harbored IDC‐P patterns 1 and 2, respectively. Patients with IDC‐P pattern 1 shared similar clinical outcomes to those without IDC‐P in both abiraterone and docetaxel treatment. However, against cases without IDC‐P or with IDC‐P pattern 1, patients with IDC‐P pattern 2 had markedly poorer prognosis in either abiraterone (mPSA‐PFS: 11.9 vs. 11.1 vs. 6.1 months, p < 0.001; mrPFS: 18.9 vs. 19.4 vs. 9.6 months, p < 0.001) or docetaxel (mPSA‐PFS: 6.2 vs. 6.6 vs. 3.0 months, p < 0.001; mrPFS: 15.1 vs. 12.6 vs. 5.5 months, p < 0.001) treatment. For patients without IDC‐P, docetaxel had comparable therapeutic efficacy with abiraterone. However, the efficacy of docetaxel was significantly inferior to abiraterone in patients with either IDC‐P pattern 1 (mPSA‐PFS: 6.6 vs. 11.1 months, p = 0.021; mrPFS: 12.6 vs. 19.4 months, p = 0.027) or pattern 2 (mPSA‐PFS: 3.0 vs. 6.1 months, p = 0.003; mrPFS: 5.5 vs. 9.6 months, p = 0.007).ConclusionCompared to docetaxel, abiraterone exhibited better efficacy in patients with IDC‐P of either pattern. However, IDC‐P pattern 2 responded unsatisfactorily to either abiraterone or docetaxel therapy. Novel therapeutic strategies for IDC‐P pattern 2 need further investigations.

Current Understanding and Management of Intraductal Carcinoma of the Prostate.

This review will discuss current understanding and management approaches of Intraductal carcinoma of the prostate (IDC-P). IDC-P is a histological finding characterized by neoplastic cells that expand but do not invade prostate ducts. The presence of IDC-P on a prostate biopsy is almost always associated with an invasive disease component and is independently associated with worse clinical outcomes in both early and late disease. These tumors are enriched for mutations in homologous DNA recombination repair (HRR) leading to high genomic instability. Multiparametric MRI with targeted biopsy may aid in diagnosis. Given the poor clinical outcomes associated with this histologic entity, its presence in biopsies should warrant consideration of aggressive management.

Presence of corpora amylacea among prostate cancer cells: an unrecognised feature of intraductal carcinoma of the prostate

Corpora amylacea (CA) is usually present in benign prostatic ducts and acini, and its presence is considered suggestive of negative or low-risk prostate cancer. The clinicopathological definition of CA among prostate cancer cells (CAPCCs)-described as CA entirely surrounded by invasive cancer cells-has not been discussed. As intraductal carcinoma of the prostate (IDC-P) is a well-known adverse prognostic factor in prostate cancer, this study aimed to elucidate the relationship between CAPCC and IDC-P. We enrolled 366 patients who underwent robotic-assisted radical prostatectomies between 2012 and 2018 at Aichi Medical University Hospital. All surgical specimens were independently reviewed by two genitourinary pathologists. The median age of the patients was 68.5 years; the median serum prostate-specific antigen was 6.49 ng/mL. IDC-P was observed in 143 (39.1%) patients, while the presence of CAPCC was observed in 47 cases (12.8%). Patients with CAPCC were associated with more advanced clinical and pathological T stages, as well as Gleason scores, than those without CAPCC (p=0.018, p<0.001, p=0.036). Notably, the presence of CAPCC was significantly associated with the presence of IDC-P (39 cases) and a high Gleason score compared with the absence of CAPCC (12 cases) (p<0.001 and p=0.036, respectively). The presence of CAPCC is an adverse pathological feature, often closely related to IDC-P. Therefore, CAPCC may be a surrogate finding to detect IDC-P via haematoxylin and eosin staining.

The presence of intraductal carcinoma of the prostate is closely associated with poor prognosis: a systematic review and meta-analysis.

We aimed to confirm the predictive ability of the presence of intraductal carcinoma of the prostate (IDC-P) for prognosis and the associations between IDC-P and clinicopathological parameters. Studies were identified in PubMed, Cochrane Library, EMBASE, Web of Science, and SCOPUS up to December 1, 2019. Hazard ratios (HRs) for survival data and odds ratios for clinicopathological data with 95% confidence intervals (CIs) were extracted. Heterogeneity was evaluated by the I2 value, and quality was assessed by the Newcastle–Ottawa Scale criteria. A total of 4179 patients from 13 studies were included. The results showed that IDC-P presence was significantly associated with poor progression-free survival (PFS; HR = 2.31; 95% CI: 1.96–2.73), cancer-specific survival (HR = 1.89; 95% CI: 1.28–2.77), and overall survival (HR = 2.14; 95% CI: 1.53–3.01). In the subgroup analysis, IDC-P presence was significantly associated with poor PFS in prostate cancer treated by radical prostatectomy (HR = 2.48; 95% CI: 2.05–3.00) and treated by radiotherapy (HR = 2.83; 95% CI: 1.65–4.85). Regarding clinicopathological characteristics, patients with IDC-P presence had significantly higher tumor clinical stages, Gleason scores, probabilities of lymph node invasion, positive surgical margins, and positive extraprostatic extension. Our meta-analysis indicates that the presence of IDC-P is closely associated with poor prognosis and adverse clinicopathological characteristics. Our data support the value and clinical utility of the routine detection of IDC-P by pathological examination. These conclusions need further validation, and prospective studies are needed to find better treatment modalities other than traditional first-line therapy for patients with IDC-P.

Propensity score matched comparison of docetaxel and androgen receptor axis-targeted (ARAT) agents in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate (IDC-P).

80 Background: Several studies have reported that intraductal carcinoma of the prostate (IDC-P) is a pathological adverse prognostic factor in patients with prostate cancer. However, the optimal treatment has not been established. The present study aimed to evaluate the efficacy of docetaxel and androgen receptor axis-targeted (ARAT) agents in patients with castration-resistant prostate cancer (CRPC) with IDC-P using a propensity score-matched analysis. Methods: We retrospectively identified 309 patients with CRPC from February 2007 to February 2016. They received initial androgen deprivation therapy (ADT) and after progression to CRPC, they received docetaxel or ARAT (abiraterone or enzalutamide) as the first-line life-prolonging therapy. The primary outcome of interest was OS from the time of CRPC diagnosis. We also investigated PFS from the time of docetaxel or ARAT initiation. Results: Propensity score-matching identified 85 patients in each group. There were no significant differences in patient characteristics between the groups. The median OS in the docetaxel group was 38.2 months versus 58.3 months in the ARAT group (HR 0.57; 95% CI 0.37–0.89; P =.01). Regarding patients with IDC-P, OS was significantly longer in the ARAT group than the docetaxel group (HR 0.48; 95% CI 0.26–0.86; P =.01), and there was no significant difference in each group, as in patients without IDC-P (HR 0.75; 95% CI 0.37–1.52; P =.43). The median PFS in the docetaxel group was 6.7 versus 7.8 months in the ARAT group (HR 0.65; 95% CI 0.45–0.94; P =.02). A multivariate analysis demonstrated that the presence of IDC-P, duration of primary ADT, visceral metastasis, and administration of ARAT as the first treatment for CRPC were independent prognostic factors for OS. Conclusions: Administration of ARAT as the first treatment for CRPC may prolong OS more than that of docetaxel, especially in patients with IDC-P.

Response of intraductal carcinoma of the prostate to androgen deprivation therapy predicts prostate cancer prognosis in radical prostatectomy patients.

Intraductal carcinoma of the prostate (IDC-P) has a poor prognosis and is thought to be completely resistant to current therapies, including androgen deprivation therapy (ADT). However, to date, there are no data showing direct evidence of such resistance. We retrospectively evaluated 145 patients with high-risk prostate cancer who underwent radical prostatectomy (RP) with neoadjuvant ADT between 1991 and 2005. All patient data were collected from slides prepared from needle biopsy (NB) samples of prostate tissue and RP specimens. Data were analyzed in terms of serum level of prostate specific antigen (PSA), Gleason score of NB samples, clinical T stage, the positive cancer core rate, maximum cancer extension rate, presence of Gleason pattern 5, and presence of IDC-P in both NB samples and RP specimens. The median initial PSA was 33.2 ng/mL (range, 2.4-296 ng/mL), and the median follow-up period was 109 months (range, 11-257 months). The preoperative median ADT period was 4 months (range, 1-20 months). IDC-P was present in 53 patients (37%) in NB samples and 65 (45%) in RP. The patients were divided into three groups based on the presence or absence of IDC-P in NB/RP samples (IDC-P-negative at biopsy: 92 cases, IDC-P-positive at biopsy with IDC-P disappearance: 15 cases, and IDC-P-positive at biopsy with IDC-P persistence: 38 cases). Overall, 28% of IDC-P-positive cases in NB samples showed the disappearance of IDC-P at RP. IDC-P persistence cases showed the poorest prognosis, while IDC-P disappearance cases had a similar prognosis to that of IDC-P-negative at biopsy cases in terms of disease-free survival, cancer-specific survival, and overall survival (P = .0018, P = .0087, and P = .0034, respectively). Some cases with IDC-P responded to ADT and demonstrated favorable clinical outcomes similar to those of cases without IDC-P. These findings indicate that cases with IDC-P are heterogeneous.

Prognostic significance of the presence of intraductal carcinoma of the prostate and bone metastasis in needle biopsy for prostate carcinoma patients with Grade Group 5

Intraductal carcinoma of the prostate (IDC-P) and bone metastasis have been both identified to associate with unfavorable clinical outcome of the prostate carcinoma (PCa). Our objective is to examine whether IDC-P or bone metastasis at diagnostic biopsies was associated with each other and whether they were linked with overall survival (OS) and cancer specific survival (CSS) of Grade Group 5 patients. We retrospectively selected the prostate biopsy specimens of 120 PCa patients with Grade Group 5 from Qilu Hospital of Shandong University between 2012 and 2016. There were 12 patients with IDC-P only, 52 patients with bone metastasis only and 10 patients with both IDC-P and bone metastasis. Overall, there was a significant correlation between the presences of the IDC-P and bone metastasis (P = 0.003). Kaplan-Meier survival analysis demonstrated that the presence of IDC-P and bone metastasis in diagnostic needle biopsy both conferred unfavorable CSS of Grade Group 5 patients. In addition, the presence of bone metastasis was a poor predictor of OS. Univariate and multivariate analysis revealed that bone metastasis was an independent prognostic factor for OS of Grade Group 5 patients, but IDC-P failed to be significant for either OS or CSS. Collectively, our study suggested that bone metastasis is an important prognostic factor and superior than the presence of the IDC-P for PCa patients with Grade Group 5.

The impact of intraductal carcinoma of the prostate on the grade group system.

34 Background: The 2014 International Society of Urological Pathology (ISUP) and WHO 2016 classifications proposed a new grade group system for prostate cancer. Intraductal carcinoma of the prostate (IDC-P) is newly recognized on them and is reported to be strongly associated with high-grade and high-volume invasive prostate cancer. Although the presence of the IDC-P influences biochemical failure in radical prostatectomy patients, no data are available regarding the significance of IDC-P in integrating to the classification grade group system. The aim of this study is to enhance the utility of grade group system integrating into the presence of IDC-P. Methods: We retrospectively evaluated 1019 patients with prostate cancer who underwent radical prostatectomy without neoadjuvant or adjuvant therapy at the hospitals that the authors were affiliated with between 2005 and 2013. Data on age, PSA level at diagnosis, clinical T stage (cT), pathological T stage (pT), presence of Gleason pattern 5 (GP5), presence of IDC-P, and surgical margin status were analyzed to predict PSA recurrence after prostatectomy. Results: The median patient age was 67 (range, 45–80) years. The median initial PSA was 6.8 ng/ml (range, 0.4–82 ng/ml). The median follow-up period was 82 (range, 0.7–148) months. IDC-P was detected in 157 patients (15.4%). Among these patients, IDC-P positive rate increased correlated with upgrading. The grade group were as follows: Group 1 without IDC-P, 16.0% (n=163); Group 2 without IDC-P, 46.1% (n=470); Group 3 without IDC-P, 15.7% (n=160); Group 4 without IDC-P, 2.6% (n=27); and Group 5 without IDC-P, 4.1% (n=42); Group 2 with IDC-P, 2.9% (n=29); Group 345 with IDC-P, 12.6% [n=128; Group 3 (n=60); Group 4 (n=13); Group 5 (n=55)] Group 3, 4, and 5 with IDC-P showed a significantly worse prognosis than any other groups without IDC-P and Group 2 with IDC-P (p&lt;.0001). In a multivariate analysis, integrating IDC-P into ISUP Grade, PSA level at diagnosis, and surgical margin status significantly predicted the prognosis (P &lt; .0001). Conclusions: Integrating the presence of IDC-P into the grade group system will improve the accuracy of patients’ outcome prediction.

Efficacy of docetaxel and androgen receptor axis-targeted agents in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate.

150 Background: This study aimed to investigate the efficacy of docetaxel and androgen receptor axis-targeted (ARAT) agents in castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P). Methods: We retrospectively identified 311 CRPC patients from June 2002 to February 2016. All patients were initially administered with androgen deprivation therapy (ADT), followed by docetaxel or ARAT (abiraterone or enzalutamide) after progressing to CRPC. The primary outcome of interest was overall survival (OS) from the time of CRPC diagnosis and progression-free survival (PFS) from the time of administration of docetaxel or ARAT. Results: IDC-P was found in 180 of 311 patients. The median OS was 33.4 and 64.0 months with and without IDC-P, respectively (hazards ratio [HR], 2.14; P &lt; 0.001). For the first treatment for CRPC, docetaxel was administered to 71 and 50 patients with and without IDC-P, respectively, with a median OS of 30.4 and 64.0 months, respectively (HR, 2.62; P &lt; 0.001). ARAT was administered to 109 and 81 patients with and without IDC-P, respectively, with a median OS of 45.0 and 69.9 months, respectively (HR, 1.84; P = 0.017). Regarding patients with IDC-P, the OS in patients who were administered with ARAT was longer than that in those administered with docetaxel (HR, 0.58; P = 0.008). The median PFS was 7.5 and 12.1 months with and without IDC-P, respectively (HR, 1.36; P = 0.03). Multivariate analysis showed that the prognostic factors for OS were the presence of IDC-P (HR, 1.91; P &lt; 0.001), and administration of ARAT (HR, 0.66; P = 0.02). Conclusions: The presence of IDC-P is an independent prognostic factor for OS and PFS in CRPC patients. ARAT may prolong OS in CRPC patients with IDC-P.

The efficacy of enzalutamide for castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P).

209 Background: Enzalutamide (ENZ) was approved to prolong survival for castration-resistant prostate cancer (CRPC) patients before and after chemotherapy. No factor was identified to predict the effectiveness of ENZ so far. .Intraductal carcinoma of the prostate (IDC-P) was newly recognized on 2017 EAU guideline and considering as a poor prognostic factor、although there has been no reports to predict the therapeutic effects of ENZ according to the presence of IDC-P. In this study, we evaluated the efficacy of ENZ for CRPC patients with or without IDC-P. Methods: We retrospectively identified 199 CRPC patients treated with ENZ from 2014 to 2018 in author-affiliated hospitals. All needle biopsy slides were reviewed by a single genitourinary pathologist and IDC-P was defined according to the criteria of McNeal at initial biopsy. Endpoint is overall survival (OS) from the time of CRPC diagnosis and time to treatment failure of ENZ. PSA response is defined as over 50% PSA decline from baseline. Results: The median patient age was 71 (range, 49–90) years. The median initial PSA was 154 ng/ml (range, 3.9–24736 ng/ml). The patients who received docetaxel were 42/199 (21%). IDC-P was detected in 98 patients (49%) at initial prostate biopsy. PSA response was 70.5% in patients without IDC-P and 53.9% in patients with IDC-P. The median OS from the time of CRPC was 37.9 and 71.5 months with and without IDC-P, respectively (P=0.013). There was no significant difference on OS in CRPC patients with IDC-P between before and after docetaxel (P=0.941). Same result was observed in CRPC patients without IDC-P (P=0.86). In time to treatment failure by ENZ, patients with IDC-P showed worse prognosis than patients without IDC-P after docetaxel (P=0.068). On the other hand, the difference disappeared before docetaxel regardless the presence of IDC-P (P=0.94). Conclusions: IDC-P is a poor prognostic factor for CRPC patients treated with ENZ. ENZ may be most effective for CRPC patients with IDC-P before chemotherapy.

Efficacy of docetaxel in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate.

This study aimed to investigate the efficacy of docetaxel in castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P). We retrospectively identified 79 CRPC patients with distant metastasis at initial diagnosis from June 2002 to January 2014. All patients received initial androgen deprivation therapy and 46 received docetaxel chemotherapy after progressing to CRPC. The primary outcome of interest was cancer-specific survival (CSS) from the time of CRPC diagnosis. The Cox regression model was used to confirm whether IDC-P and docetaxel would act as independent factors for prognosis. IDC-P was found in 62 of 79 patients. The median CSS in the IDC-P-present group was 18.2 versus 45.6months in the IDC-P-absent group (HR 2.67; 95% CI 1.18 to 6.06; P=0.019). Docetaxel was administered to 36 patients with IDC-P and 10 patients without IDC-P, with a median CSS of 20.5 versus 53.2months, respectively (HR 2.98; 95% CI 1.02 to 8.64; P=0.044). Multivariate analysis demonstrated that the presence of IDC-P and docetaxel were independent prognostic factors for CSS (P=0.026 and 0.005, respectively) and overall survival (OS) (P=0.029 and 0.001, respectively). The presence of IDC-P is an independent prognostic factor in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis. Docetaxel may prolong CSS and OS in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis.

Prognostic parameter for high risk prostate cancer patients at initial presentation.

High-risk prostate cancer can be defined by a patient's Gleason score (GS), prostate-specific antigen (PSA) level, and clinical T (cT) stage, but a novel marker is needed due to heterogeneity of the disease. In this study, we evaluated whether intraductal carcinoma of the prostate (IDC-P) confirmed by needle biopsy is an adverse prognostic parameter for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with high-risk prostate cancer. We retrospectively evaluated 204 patients with high-risk prostate cancer treated by radical prostatectomy from 1991 to 2005 at Nagoya University and its affiliated hospitals. Data on each patient's PSA level, biopsy GS, cT stage, presence of Gleason pattern 5, presence of IDC-P, percentage of the core involved with cancer, and maximum percentage of the core involved with cancer were analyzed. The median follow-up period was 108 months (range, 11-257 months). Forty-eight patients (24%) showed disease progression. Thirty-four patients (17%) died of the disease during follow-up. The IDC-P component was detected in 74 (36%) needle biopsy samples. The 5-, 10-, and 15-year CSS rates of the IDC-P-negative cases were 3.2%, 9.0%, and 23.7%; the corresponding rates of the IDC-P-positive cases were 23.9%, 33.7%, and 52.7%, respectively (P = 0.0001). In the Fine and Gray's model for PFS, IDC-P, maximum percentage of the core involved with cancer, and cT stage were significantly associated (P = 0.013, P = 0.003, P = 0.007). In the Fine and Gray's model for CSS, only IDC-P was significant (P = 0.027). In a multivariate Cox regression analysis, IDC-P (P = 0.04; hazard ratio [HR], 1.95) and maximum percentage of the core involved with cancer (P = 0.021; HR, 0.43) were significant factors in predicting overall survival (OS). The presence of IDC-P in a needle biopsy was a prognostic factor for PFS, CSS, and OS in patients with high-risk prostate cancer who underwent radical prostatectomy. Multimodal pre-and/or post- surgical therapy may be needed when IDC-P is found in a needle biopsy specimen.

Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells.

To determine the relevance of intraductal carcinoma of the prostate (IDC-P) in advanced prostate cancer by first examining whether IDC-P was originally present in patients who later developed advanced prostate cancer and then using patient-derived xenografts (PDXs) to investigate the response of IDC-P to androgen deprivation therapy (ADT). We conducted a retrospective pathology review of IDC-P in primary prostate biopsy or surgery specimens from 38 men who subsequently developed advanced prostate cancer. Overall survival was calculated using the Kaplan-Meier method. To demonstrate the response of IDC-P to ADT, we established PDXs from seven patients with familial and/or high-risk sporadic prostate cancer. After castration and testosterone restoration of host mice, we measured the volume and proliferation of IDC-P within PDX grafts. We found that IDC-P was a prominent feature in the primary prostate specimens, present in 63% of specimens and often co-existing with poorly differentiated adenocarcinoma. Overall survival was similar in patients with or without IDC-P. In the PDXs from all seven patients, IDC-P was identified and present at a similar volume to adenocarcinoma. Residual IDC-P lesions persisted after host castration and, similar to castrate-tolerant adenocarcinoma, testosterone restoration led to tumour regeneration. The study showed that IDC-P is prevalent in aggressive prostate cancer and contains cells that can withstand androgen deprivation. Thus, IDC-P appears functionally relevant in advanced prostate cancer. The presence of IDC-P may be a trigger to develop innovative clinical management plans.

Intraductal Carcinoma of the Prostate: A Risk for Rapid Recurrence

Intraductal carcinoma of the prostate (IDC-P), recently defined by the World Health Organization in 2016, is a distinct histologic entity associated with an aggressive clinical course, including increased risk of biochemical recurrence, metastasis, and mortality. Differential diagnosis includes intraductal spread of urothelial carcinoma, prostatic ductal carcinoma, and high-grade prostatic intraepithelial neoplasia. BRCA mutations are associated with an increased risk of IDC-P. The presence of IDC-P on initial biopsy or radical prostatectomy should trigger aggressive treatment and should be considered a contraindication to active surveillance, regardless of tumor volume.

Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study.

Intraductal carcinoma of the prostate (IDC-P) is a distinct histopathologic feature associated with high-grade, advanced prostate cancer. Although studies have shown that IDC-P is a predictor of progression following surgical or radiation treatment for prostate cancer, there are sparse data regarding IDC-P on diagnostic needle biopsy as a prognosticator of prostate cancer mortality. This was a population-based study of all prostate cancer patients diagnosed using needle biopsy and without evidence of systemic disease between 1991 and 1999 within a defined geographic region of Norway. Patients were identified by cross-referencing the Norwegian Cancer Registry. Of 318 eligible patients, 283 had biopsy specimens available for central pathology review. Clinical data were obtained from medical charts. We examined whether IDC-P on diagnostic needle biopsy was associated with adverse clinicopathological features and prostate cancer mortality. Patients with IDC-P on diagnostic needle biopsy had a more advanced stage and a higher Gleason score compared to patients without IDC-P. IDC-P was also associated with an intensively reactive stroma. The 10-year prostate cancer-specific survival was 69% for patients with IDC-P on diagnostic needle biopsy and 89% for patients without IDC-P (Log rank P-value < 0.005). The presence of IDC-P on diagnostic needle biopsy remained an independent predictor of prostate cancer mortality after adjustments for clinical prognostic factors and treatment. After adjustment for the newly implemented Grade Group system of prostate cancer, IDC-P showed a strong tendency toward statistical significance. However, IDC-P did not remain a statistically significant predictor in the multivariable analysis. IDC-P on diagnostic needle biopsy is an indicator of prostate cancer with a high risk of mortality. Accordingly, a diagnosis of IDC-P on needle biopsy should be reported and considered a feature of high-risk prostate cancer. Moreover, the association between IDC-P and reactive stroma provides evidence in support of the idea that stromal factors facilitate carcinoma invasion to the prostatic acini and ducts. Prostate 77:859-865, 2017. © 2017 Wiley Periodicals, Inc.