Intraductal Carcinoma Of Prostate Research Articles

Clinical utility of IDC-P (intraductal carcinoma of the prostate) in the decision making of initial treatment for metastatic hormone-sensitive prostate cancer.

93 Background: In recent years, the usefulness of using androgen receptor axis-targeted agents (ARAT) such as abiraterone, enzalutamide, and apalutamide for metastatic hormone-sensitive prostate cancer (mHSPC) in the up-front setting has been demonstrated. However, it is still unclear which patients could truly benefit from these treatments. On the other hand, intraductal carcinoma of prostate (IDC-P) is a known poor prognostic factor for prostate cancer patients. In the present study, we investigated the association between the presence of IDC-P and therapeutic response to mHSPC. Methods: This retrospective analysis included 318 patients with mHSPC from thirteen affiliated institutions between 2014 and 2021, and evaluated biopsy specimens for the presence of IDC-P. All patients were grouped by their first-line treatment, either ARAT (n=100, receiving a combination of androgen-deprivation therapy [ADT] and ARAT), or conventional therapy (n=218, receiving ADT with or without standard antiandrogen agents). We compared overall survival (OS) and second progression-free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC-P to evaluate whether presence of IDC-P predicts response to each treatment. The PFS2 was defined as the period from diagnosis of mHSPC to disease progression on second-line therapy or death. Propensity score matching was used for one-to-one nearest neighbor matching in order to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of patients were well balanced after propensity score matching. Results: Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD-P positive. In the propensity score-matched cohort, OS and PFS2 of IDC-P positive cases were significantly prolonged in the ARAT group compared to the conventional group (OS: hazard ratio [HR], 0.36; p=0.047; PFS2: HR, 0.30; p<0.001). In contrast, IDC-P negative cases did not show a difference in OS and PFS2 between the ARAT and the conventional groups (OS: HR, 1.09; p=0.920; PFS2: HR, 0.40; p=0.264). Conclusions: The findings highlight a high prevalence of IDC-P among patients with mHSPC and suggest that IDC-P may be a reliable indicator to implement ARAT as first-line therapy.

WHO Classification of Tumours fifth edition: evolving issues in the classification, diagnosis, and prognostication of prostate cancer.

The fifth edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems encompasses several updates to the classification and diagnosis of prostatic carcinoma as well as incorporating advancements in the assessment of its prognosis, including recent grading modifications. Some of the salient aspects include: (1) recognition that prostatic intraepithelial neoplasia (PIN)‐like carcinoma is not synonymous with a pattern of ductal carcinoma, but better classified as a subtype of acinar adenocarcinoma; (2) a specific section on treatment‐related neuroendocrine prostatic carcinoma in view of the tight correlation between androgen deprivation therapy and the development of prostatic carcinoma with neuroendocrine morphology, and the emerging data on lineage plasticity; (3) a terminology change of basal cell carcinoma to “adenoid cystic (basal cell) cell carcinoma” given the presence of an underlying MYB::NFIB gene fusion in many cases; (4) discussion of the current issues in the grading of acinar adenocarcinoma and the prognostic significance of cribriform growth patterns; and (5) more detailed coverage of intraductal carcinoma of prostate (IDC‐P) reflecting our increased knowledge of this entity, while recommending the descriptive term atypical intraductal proliferation (AIP) for lesions falling short of IDC‐P but containing more atypia than typically seen in high‐grade prostatic intraepithelial neoplasia (HGPIN). Lesions previously regarded as cribriform patterns of HGPIN are now included in the AIP category. This review discusses these developments, summarising the existing literature, as well as the emerging morphological and molecular data that underpins the classification and prognostication of prostatic carcinoma.

Radiomic Machine Learning and External Validation Based on 3.0 T mpMRI for Prediction of Intraductal Carcinoma of Prostate With Different Proportion.

PurposeTo assess the association of radiomics features based on multiparametric MRI (mpMRI) with the proportion of intraductal carcinoma of prostate (IDC-P) and validate the predictive models.Materials and MethodsWe retrospectively included pre-treatment MR images of prostate cancer (PCa) with IDC components of high proportion (≥10%, hpIDC-P), low proportion (<10%, lpIDC-P), and pure acinar adenocarcinoma (PAC) from our institution for training and internal validation and cooperated cohort for external validation. Normalized images of T2WI, diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) map, and dynamic contrast enhanced (DCE) sequences were used for radiomics modeling. The clinical model was built based on serum total prostate specific antigen (tPSA) and Gleason score (GS), and the integrated model was the combination of Rad-score and clinicopathological data. The discrimination ability was assessed by area under the receiver operating characteristic curve (ROC-AUC) in the internal and external validation sets and compared by DeLong test.ResultsOverall, 97 patients with hpIDC-P, 87 lpIDC-P, and 78 PAC were included for training and internal validation, and 11, 16, and 19 patients for external validation. The integrated model for predicting hpIDC-P got the best ROC-AUC of 0.88 (95%CI = 0.83-0.93) in internal and 0.86 (95%CI = 0.72-1.0) in external validation, which both outperformed clinical models (AUC=0.78, 95% CI = 0.72-0.85, AUC=0.69, 95% CI = 0.5-0.85, respectively) based solely on GS, and the radiomics model (AUC=0.85, 95% CI = 0.79-0.91) was slightly inferior to the integrated model and better than the clinical model in internal dataset. The integrated model for predicting lpIDC-P outperformed both radiomics and clinical models in the internal dataset, while slightly inferior to the integrated model for predicting hpIDC-P.ConclusionsRadiomics signature improved differentiation of both hpIDC-P and lpIDC-P versus PAC when compared with the clinical model based on Gleason score, and was validated in an external cohort.

Prostate cancer nomenclature at diagnosis can affect treatment decisions.

Prostate cancer nomenclature at diagnosis can affect treatment decisions.

Perils of hidden depths

A man in his 60s presented with lower urinary tract symptoms. His serum prostate-specific antigen level was 6 ng/mL. A prostate biopsy was performed (figure 1). Figure 1 Prostate biopsy...

Retrospective study on the benefit of adjuvant radiotherapy in men with intraductal carcinoma of prostate

BackgroundIntraductal carcinoma of the prostate (IDC-P) is an independent biomarker of recurrence and survival with particular treatment response, yet no study has tested its response to radiotherapy. The aim of our project was to test the impact of adjuvant radiotherapy (ART) in patients with localized to locally advanced prostate cancer (PC) and IDC-P.Materials and methodsWe performed a retrospective study of men with pT2-T3 PC treated by radical prostatectomy (RP) with or without ART, from two centres (1993–2015). Exclusion criteria were the use of another type of treatment prior to biochemical recurrence (BCR), and detectable prostate- specific antigen (PSA) following RP or ART. Primary outcome was BCR (2 consecutive PSA ≥ 0.2 ng/ml). Patients were grouped by treatment (RPonly/RP + ART), IDC-P status, and presence of high-risk features (HRF: Grade Groups 4–5, positive margins, pT3 stage).ResultsWe reviewed 293 RP specimens (median follow-up 99 months, 69 BCR). Forty-eight patients (16.4%) were treated by RP + ART. Multivariate Cox regression for BCR indicated that IDC-P had the strongest impact (hazard ratio [HR] = 2.39, 95% confidence interval [CI]:1.44–3.97), while ART reduced the risk of BCR (HR = 0.38, 95%CI: 0.17–0.85). Other HRF were all significant except for pT3b stage. IDC-P[+] patients who did not receive ART had the worst BCR-free survival (log-rank P = 0.023). Furthermore, IDC-P had the same impact on BCR-free survival as ≥1 HRF (log-rank P = 0.955).ConclusionMen with IDC-P who did not receive ART had the highest BCR rates, and IDC-P had the same impact as ≥1 HRF, which are often used as ART indications. Once validated, ART should be considered in patients with IDC-P.

Intraductal Carcinoma of Prostate (IDC-P), Grade Group, and Molecular Pathology: Recent Advances and Practical Implication

The Gleason grading system for prostatic carcinoma is widely used internationally and is based on microscopic architectural patterns of tumors. Over the years, there have been modifications to the original grading system established by Donald F Gleason in 1966 and refined in 1974 which have subsequently been established by the World Health Organization in its WHO Classification of Tumors of the Urinary System and Male Genital Organs book, published in 2016. There have been certain practical issues associated with the changes, of note, the addition of intraductal carcinoma of prostate (IDC-P), which unlike its breast counterpart rarely occurs in isolation without association with invasive carcinoma and tends to be associated with high-grade invasive carcinoma. In addition, the Grade group system has been introduced which categorizes tumors into prognostically relevant groups based on the histological grade scores. The grade group system brings to light the importance of making accurate scoring and subsequent grouping of the tumors as it affects the clinical treatment, prognostic implication and stage assignment. Molecular pathology of the prostate is not widely utilized in clinical practice, but is emerging. The most common genomic aberration in prostate cancer includes gene fusion, amplification, deletion, and mutation. In addition, up and down regulation of gene expression in critical cellular pathways is also at play. A series of long noncoding RNA expression changes have been also unveiled from transcriptome sequencing data. They play a regulatory role in prostate cancer and are promising diagnostic and potentially prognostic markers as well as molecular treatment strategy. In this review, we summarize recent advances in molecular pathology of prostate cancer and their emerging clinical utility with currently available molecular tests. In this review article, we discuss the followings: 1) Gleason grading system with its modification, 2) Grade group, 3) Intraductal carcinoma, and 4) molecular pathology. Additionally, we present that molecular studies continue to emerge, and there is significant opportunity for targeted therapeutic options that remains to be explored in depth.

The prognostic role of IDC-P in mCRPC and its predictive value in those treated with docetaxel or abiraterone as first-line therapy.

e603 Background: Intraductal carcinoma of prostate (IDC-P) is recognized as a newly pathological entity in 2016. Its role in metastatic castration-resistant prostate cancer (mCRPC) remains unknown. The aim of this study is to explore the association of IDC-P with clinical outcomes and to further identify its potential predictive role in making first-line treatment decision for mCRPC patients. Methods: We retrospectively analyzed data of 131 men with mCRPC. IDC-P was diagnosed by re-biopsy at the time of mCRPC. After mCRPC, 45 and 41 patients received abiraterone (Abi) or docetaxel (Doc) as first-line therapy, respectively. PSA response, PSA progression-free survival (PSA-PFS) and overall survival (OS) from mCRPC to death were analyzed. Kaplan-Meier curves, log-rank test, Cox regression models and Harrell’s C-index were conducted to analyze disease progression, treatment efficacy and outcomes. Results: The incidence of IDC-P in mCRPC reached to 47.3%. IDC-P was not only related to rapid PSA progression, but also associated with 20-month decrease of OS. Among IDC-P(-) patients, PSA response, PSA-PFS and OS were comparable in Abi-treated and Doc-treated groups. In contrast, among IDC-P(+) patients, PSA response rate is higher in Abi-treated vs. Doc-treated group (52.4% vs. 21.7%; p = 0.035), also, PSA-PFS and OS were much longer in Abi-treated group (PSA-PFS:13.5 vs.6.0 months, p = 0.012; OS:23.6 vs.14.7 months, p = 0.128). Cox regression indicated that, for IDC-P(+) patients, Abi was associated with prolonged time of PSA-PFS (HR = 0.33, 95%CI: 0.14-0.79, p = 0.013), and could significantly increase the predictive accuracy of standard model, with an obvious increase of the C-index from 0.719 to 0.778 (p = 0.009). Conclusions: The presence of IDC-P in mCRPC from re-biopsy was not only an independent prognosticator for clinical outcomes, but also strongly associated with poor response to Doc-based chemotherapy. We also found that IDC-P status could be considered as a novel predictive marker in helping physicians precluding Doc as first-line therapy in IDC-P(+) patients. Also, these findings require large-scale prospective validation.

Intraductal carcinoma of prostate (IDC-P): from obscure to significant.

The concept of intraductal carcinoma of prostate (IDC-P) has evolved over the years and its clinicopathologic significance has come to be more clearly appreciated. In contrast to morphologically malignant intraductal lesions that represent earlier stages of the malignant process in other anatomic sites such as the breast, IDC-P has now been generally recognized as a prognostically unfavorable manifestation of later stage spreading of its invasive counterpart. We here briefly review the evolution of the IDC-P concept, the histological diagnostic criteria and differential diagnosis, the clinical significance, as well as recent molecular data of IDC-P.

Histopathological features of intra-ductal carcinoma of prostatic and high grade prostatic intraepithelialneoplasia and correlation with PTEN and P63.

The main morphologic differential diagnosis of intra-ductal carcinoma of prostate (IDC-P) is high grade prostatic intraepithelialneoplasia (HGPIN). Since IDC-P, unlike PIN, was strongly correlated with aggressive prostate cancer, differentiation of these is too necessary. So we evaluated immunohistopathological patterns and the prognostic factors of IDC-P and HGPIN, in radical prostatectomy samples. We evaluated 250 radical prostatectomy and detected 210 cases of prostatic adenocarcinoma without IDC-P foci, 40 cases with adenocarcinoma concomitant IDC-P, and 40 cases HGPIN; therefore, we evaluated immunohistopathological criteria in these groups. Data were analyzed using SPSS and P-value <0.05 was considered as the statistical significant level. PSA level was significantly higher in IDC-P compared with non-IDC-P patients (15.7 ± 3.1 vs. 10.2 ± 4.3, P = 0.041). All pathological and morphologic features, also invasions factors were higher in IDC-P compared to non-IDC-P groups (P < 0.001). P63 was positive expressed in all IDC-P and HGPIN specimen. PTEN protein was diffusely expressed in the cytoplasm of all HGPIN but in 4 (11.1%) of IDC-P. PTEN and P63 were negative in adenocarcinoma foci. We found that IDC-P had a unique histoclinical feature and was strongly associated with poor prognostic factors. Diagnosis and report of IDC-P should be considered in all prostate specimens. Also, we recommend PTEN IHC application for differentiated IDC-P from HGPIN in biopsies.

The presence and clinical implication of intraductal carcinoma of prostate in metastatic castration resistant prostate cancer.

Intraductal carcinoma of prostate (IDC-P) is always underestimated pathological pattern in prostate cancer and its role is still unclear in castration resistant prostate cancer (CRPC). This study was conducted to investigate the presence and the roles of IDC-P in patients with metastatic CRPC. 45 patients with initially diagnosed metastatic prostate cancer and then progressed to CRPC, were included. All of them were received twice transperineal biopsies at the time of initial diagnosis and the time of CRPC. All samples were retrieved to detect the presence of IDC-P. PSA doubling time (PSADT) was considered as a parameter presenting the progression of CRPC. The relationships between IDC-P and other clinicopathological variables were analyzed. IDC-P was found only in 20% (9/45) cases at initial diagnosis, whereas, it increased to 62.5% (28/45) at the time of CRPC (χ(2) = 16.568, P = 0.000). Compared to acinar adenocarcinoma components in tumor tissues, IDC-P components, especially solid subtype, had obviously poor/no response to androgen deprivation therapy (ADT). In addition, among patients treated with docetaxel-based chemotherapy (n = 24), patients with IDC-P also showed more unfavorable response than those without IDC-P (20% vs. 66.7%, P = 0.022). The presence of IDC-P and serum testosterone at the time of CRPC, were significantly associated with rapid disease progression. 13/28 (46.4%) CRPC with IDC-P had PSADT less than 30 days, while, only 1/17 (5.9%) patient without IDC-P had a less than 30 days PSADT (χ(2) = 8.114, P = 0.004). Limitations included the relative short follow-up time and a relative small cohort. The presence of IDC-P was significantly associated with rapid progression of CRPC. And its presence could suggest the poor response to initial ADT and sequential docetaxel-based chemotherapy. Detection of IDC-P should be of importance in CRPC, and re-biopsy at the time of CRPC might be one of practical solutions. The mechanism of the ADT and docetaxel resistance to IDC-P needed to be further investigated.

Is there any prognostic impact of intraductal carcinoma of prostate in initial diagnosed aggressively metastatic prostate cancer?

Intraductal carcinoma of prostate (IDC-P) was usually found to be co-exist with conventional aggressive prostate adenocarcinoma. The presence of IDC-P was considered as an adverse pathological factor, which was associated with high Gleason score, large prostate volume and accelerated disease progression. However, no any information is available on the presence of IDC-P diagnosed by needle biopsy in patients with metastatic prostate cancer. We investigated the incidence and prognostic value of intraductal carcinoma of prostate (IDC-P) in initial diagnosed metastatic prostate cancer. We included 278 patients with initial diagnosed metastatic prostate cancer treated between 2008 and 2011, all the pathological diagnosis were from ultrasonic-guided transperineal needle biopsy. IDC-P was strictly defined according to Epstein's criteria. Analyzed factors included age, Eastern Cooperative Oncology Group (ECOG) score, clinical T staging, Gleason scores, baseline prostate specific antigen (PSA), alkaline phosphatase (ALP), hemoglobin (HGB), PSA normalization, and the presence of IDC-P. Totally, IDC-P was found in 57/278 (20.5%) cases. Univariate analysis showed that, compared with cases without IDC-P, cases with IDC-P was definitely associated with much shorter CRPC-free survival (CFS) time (46.05 ± 1.39 vs. 22.98 ± 1.80 months, P = 0.000) and OS time (50.38 ± 1.18 vs. 36.43 ± 2.10 months, P = 0.000). Multivariate analysis showed that the presence of IDC-P was the only independent prognostic factor associated with poor CFS (HR = 4.886, P = 0.011) and OS (HR = 1.945, P = 0.020). Further sub-analysis showed, even among patients with higher Gleason score (≥8) (n = 158), IDC-P was still significantly and inversely associated with CFS and OS (the median CFS time: 40 versus 22 months; P = 0.000; the median OS time: 54 vs. 36 months, P = 0.000). Again, Cox's regression model confirmed that only the presence of IDC-P was still not only an independent prognostic factor predicting shorter time of CRPC (HR = 4.031, P = 0.035), but also for poorer OS (HR = 2.499, P = 0.006). The presence of IDC-P in initial diagnosed metastatic prostate cancer, even among patients with more aggressive pattern, was firstly found to be significantly and independently associated with earlier occurrence of CRPC and poorer OS. We recommended the presence of IDC-P should be a routine record in pathological report of clinical diagnosis and other potential therapeutic regimen might be added to intervene in the integrated therapy as early as possible. Prostate 75:225-232, 2015. © 2014 Wiley Periodicals, Inc.

Clinicopathological analysis of intraductal proliferative lesions of prostate: intraductal carcinoma of prostate, high-grade prostatic intraepithelial neoplasia, and atypical cribriform lesion.

Intraductal carcinoma of the prostate (IDC-P) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two distinct intraductal lesions; the former is usually associated with invasive carcinoma and has an aggressive course while the latter is considered a precancerous lesion. In addition, there are morphologically lesions not well characterized that fall between IDC-P and HGPIN, consequently termed "atypical cribriform lesions (ACLs)." Using whole mount radical prostatectomy specimens, we evaluated the relationship between these intraductal proliferative lesions and clinicopathological parameters. In this study, ACLs were characterized as a loose cribriform intraductal proliferation with greater architectural complexity when compared to HGPIN, but lacking significant nuclear pleomorphism and/or comedonecrosis. Of 901 radical prostatectomies (2006-2012), IDC-P, ACL, and HGPIN were recorded in 155, 22, 436 cases, respectively. Patients with IDC-P showed more aggressive pathologic features when compared to HGPIN. Invasive cancers in patients with ACL had higher Gleason score (P=.00016), larger tumor volume (P=.025), and more advanced pT stage (P=.023) than those with HGPIN. Cases with ACL showed a higher risk of biochemical recurrence than those with HGPIN and a lower risk than those with IDC-P based on log-rank tests (P=.0045 and P=.0069, respectively). In multivariate analysis, the presence of HGPIN was identified as an independent predictor for infrequent biochemical recurrence (P=.0058). We confirmed IDC-P as a marker of adverse pathologic features and clinical aggressiveness. Our results suggest that ACL should be distinguished from HGPIN and these lesions mandate active clinical surveillance.

Intraductal carcinoma of prostate (IDC-P) and high-grade prostatic intraepithelial neoplasia (HGPIN) in prostate biopsy: why we should distinguish one from the other

<h3>Aims</h3> To explore the distinction between Intraductal carcinoma of prostate (IDC-P) and high-grade prostatic intraepithelial neoplasia (HGPIN). <h3>Methods</h3> A case of IDC-P is presented with review of literature. <h3>Results</h3> Transurethral resection of prostate showed extensive IDC-P associated with a smaller component of Gleason pattern 5+5 adenocarcinoma. HGPIN was not identified. Prostate biopsies performed immediately prior were reported as HGPIN associated with Gleason pattern 5+5 adenocarcinoma. <h3>Discussion</h3> IDC-P is an uncommon entity characterised by malignant cells that fill and expand pre-existing prostatic ducts and glands, with an intact basal cell layer, featuring cribriform or solid pattern with or without comedonecrosis.¹ Morphological criteria have been proposed to distinguish IDC-P from several other lesions including HGPIN.^1,2 IDC-P and HGPIN are biologically distinct entities supported by emerging molecular data and leading to differences in patient management.^1,2 While HGPIN is postulated to be an early precursor lesion in some carcinomas, IDC-P almost always co-exists with aggressive prostate cancer in radical prostatectomy featuring higher Gleason score, larger tumour volume, greater risk of extra-prostatic extension, seminal vesicle invasion and pelvic lymph node metastasis.^2–4 It is crucial to recognise IDC-P, particularly as an isolated finding in prostate biopsies, in order to implement immediate definitive therapy for high grade carcinoma even in the absence of invasion.^1–4

Erratum: Correction of Author Name. Intraductal Carcinoma of Prostate: A Comprehensive and Concise Review

To the Editor: We found an error in our published article. Roberts JA, Zhou M, Park YW, Ro JY. Intraductal Carcinoma of Prostate: A Comprehensive and Concise Review. Korean J Pathol 2013; 47(4): 307-15. http://dx.doi.org/10.4132/KoreanJPathol.2013.47.4.307. The author's name was misspelled. The author list should be corrected as follows. Corrected Author List Jordan A. Roberts1·Ming Zhou2·Yong Wook Park3·Jae Y. Ro1,4

Intraductal Carcinoma of Prostate: A Comprehensive and Concise Review

Intraductal carcinoma of the prostate (IDC-P) is defined as a proliferation of prostate adenocarcinoma cells distending and spanning the lumen of pre-existing benign prostatic ducts and acini, with at least focal preservation of basal cells. Studies demonstrate that IDC-P is strongly associated with high-grade (Gleason grades 4/5), large-volume invasive prostate cancers. In addition, recent genetic studies indicate that IDC-P represents intraductal spread of invasive carcinoma, rather than a precursor lesion. Some of the architectural patterns in IDC-P exhibit architectural overlap with one of the main differential diagnoses, high-grade prostatic intraepithelial neoplasia (HGPIN). In these instances, additional diagnostic criteria for IDC-P, including marked nuclear pleomorphism, non-focal comedonecrosis (>1 duct showing comedonecrosis), markedly distended normal ducts/acini, positive nuclear staining for ERG, and cytoplasmic loss of PTEN by immunohistochemistry, can help make the distinction. This distinction between IDC-P and HGPIN is of critical importance because IDC-P has an almost constant association with invasive carcinoma and has negative clinical implications, including shorter relapse-free survival, early biochemical relapse, and metastatic failure rate after radiotherapy. Therefore, IDC-P should be reported in prostate biopsies and radical prostatectomies, regardless of the presence of an invasive component. This article will review the history, diagnostic criteria, molecular genetics, and clinical significance of IDC-P.

In situ and intraductal epithelial proliferations of prostate: definitions and treatment implications

• High-grade prostatic intraepithelial neoplasia (HGPIN) is an intracellular proliferation of ductal epithelial cells. On its own, the presence of HGPIN does not warrant active intervention. • In contrast, intraductal carcinoma of prostate and prostatic ductal adenocarcinoma of prostate are markers of aggressive prostatic adenocarcinoma. • The presence of even small foci of these tumours on biopsy warrants immediate intervention, even in the absence of demonstrable invasive disease. • This second part of the review of in situ epithelial proliferations of the prostate looks at these conditions in more detail.