The impact of intraductal carcinoma of the prostate on the site and timing of recurrence and cancer‐specific survival

Trinh, Vincent Q.; Sirois, Jennifer; Benzerdjeb, Nazim; Mansoori, Babak Khoshkrood; Grosset, Andrée-Anne; Albadine, Roula; Latour, Mathieu; Mes‐Masson, Anne‐Marie; Hovington, Hélène; Bergeron, Alain; Ladouceur, Martin; Fradet, Yves; Saad, Fred; Trudel, Dominique

doi:10.1002/pros.23513

Cited by 27 publications

(16 citation statements)

References 27 publications

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“…Our group reported that IDC‐P is an adverse prognostic factor for patients with high‐risk or metastatic PCa patients . A recent paper pointed out the higher tendency of distant metastasis rather than local recurrence in IDC‐P‐positive patients at the first clinical detection of recurrence and that it influenced cancer‐specific survival . Molecular evidence also supports the association of a TMPRESS2‐ERG genomic change and the heterozygosity of RB1 and TP53 in patients with IDC‐P .…”

Section: Introductionsupporting

confidence: 62%

The influence of the presence of intraductal carcinoma of the prostate on the grade group system's prognostic performance

et al. 2019

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Background Although the presence of intraductal carcinoma of the prostate (IDC‐P) influences biochemical failure in radical prostatectomy patients, no data are available regarding the impact of its integration into the classification grade group system. Thus, the aim of this study was to enhance the utility of the grade group system by integrating the presence of IDC‐P. Methods This study was a retrospective evaluation of 1019 patients with prostate cancer who underwent radical prostatectomy between 2005 and 2013 without neoadjuvant or adjuvant therapy. The data on age, prostate‐specific antigen (PSA) level at diagnosis, 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 and the median initial PSA level was 6.8 (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, the increase in the positive rate of IDC‐P correlated with tumor upgrading. The grade groups (GGs) were as follows: GG1 without IDC‐P, 16.0% (n = 163); GG2 without IDC‐P, 46.1% (n = 470); GG3 without IDC‐P, 15.7% (n = 160); GG4 without IDC‐P, 2.6% (n = 27); GG5 without IDC‐P, 4.1% (n = 42); any GG with IDC‐P, 15.4% [n = 157; GG 2 (n = 29); GG3 (n = 60); GG4 (n = 13); GG5 (n = 55)]. Any grade Group with IDC‐P showed significantly worse prognosis than any other group without IDC‐P (P < 0.0001). In a multivariate analysis, integration of the IDC‐P into the Grade Groups, the PSA level at diagnosis, and the surgical margin status were significant prognostic predictors (P < 0.0001, < 0.0001 and < 0.0001, respectively). Conclusions Integrating the presence of IDC‐P into the grade group system will result in more accurate predictions of patient outcome.

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Section: Introductionsupporting

confidence: 62%

The influence of the presence of intraductal carcinoma of the prostate on the grade group system's prognostic performance

et al. 2019

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“…Whether IDC-P is a harbinger of aggressive, advanced disease or a precursor lesion is important for risk stratification among PCa patients and for determining aggressiveness of subsequent therapy. For example, recent data have demonstrated a benefit of adjuvant radiation therapy in patients with IDC-P [57]; while definitive therapy is certainly prudent, such additional adjuvant therapy would likely be overtreatment after RP in cases with iIDC-P. Additionally, we demonstrate that iIDC-P may have a distinct molecular pathogenesis from conventional PCa, and one that may lend itself to targeted therapies, should these cancers be identified in a progressed state. In this context, targeted sequencing of could be potentially beneficial, although identifying advanced PCa that may have originated as iIDC-P remains a challenge.…”

Section: Discussionmentioning

confidence: 61%

Intraductal carcinoma of the prostate in the absence of high‐grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations

Khani

Wobker

Hicks

et al. 2019

The Journal of Pathology

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Intraductal carcinoma of the prostate (IDC‐P) most often appears associated with high‐grade invasive prostate carcinoma (PCa), where it is believed to represent retrograde spread. However, IDC‐P rarely occurs as an isolated finding at radical prostatectomy or with concurrent low‐grade (Grade Group 1) invasive carcinoma. We hypothesized that isolated IDC‐P (iIDC‐P) in these unusual cases may represent a distinct in situ lesion and molecularly profiled 15 cases. iIDC‐P was characterized by copy number alteration (CNA) profiling and targeted next generation sequencing in cases with sufficient tissue (n = 7). Immunohistochemistry for PTEN and ERG was performed on the total cohort (n = 15), where areas of iIDC‐P and associated invasive disease were evaluated separately (n = 9). By copy number profiling, iIDC‐P alterations were similar to those previously described in high‐grade invasive PCa (PTEN, RB1, and CHD1 loss; MYC gain). However, in four cases, targeted sequencing revealed a striking number of activating oncogenic driver mutations in MAPK and PI3K pathway genes, which are extraordinarily rare in conventional PCa. In addition, pathogenic mutations in DNA repair genes were found in two cases of iIDC‐P (BRCA2, CHEK2, CDK12) and other known PCa‐associated mutations (FOXA1, SPOP) in two cases. Overall, ERG was expressed in 7% (1/15) of the iIDC‐P lesions and PTEN was lost in 53% (8/15). Discordance for ERG or PTEN status between IDC‐P and the low‐grade PCa was observed in five of nine cases, with intact PTEN in the invasive tumor and PTEN loss in IDC‐P in four. Despite a CNA profile similar to conventional PCa, iIDC‐P is enriched with potentially targetable oncogenic driver mutations in MAPK/PI3K genes. Based on PTEN and ERG status, iIDC‐P is not likely a precursor to the associated low‐grade invasive PCa, but represents a molecularly unique in situ tumor of unclear clinical significance. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…Table 1 shows the characteristics of the included studies. [11][12][13][14][15][16][17][18][19][20][21][22][23] These studies were published between 2010 and 2019. A total of 4179 patients from 6 countries including Portland, Canada, Japan, America, China and Norway were enrolled.…”

Section: Study Characteristicsmentioning

confidence: 99%

The Presence of Intraductal Carcinoma of The Prostate Is Closely Correlated with Poor Prognosis: A Systematic Review and Meta-Analysis

Zhang

Sun

et al. 2020

Preprint

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Background We aimed to confirm the predictive ability of the presence of intraductal carcinoma of the prostate (IDC-P) on prognosis and association between IDC-P and clinicopathological parameters.Methods Literatures were identified in PubMed, Cochrane Library, etc. up to December 1st, 2019. Hazard ratio (HR) for survival data and odds ratio (OR) for clinicopathological data with 95% confidence interval (CI) were extracted. Heterogeneity was evaluated by I 2 value and quality assessment by Newcastle-Ottawa Scale (NOS) criteria.Result A total of 4179 patients from 13 studies were included. The results showed IDC-P presence was significantly associated with poor progression-free survival (PFS) (HR = 2.31; 95% CI 1.96 to 2.73), cancer-specific survival (CSS) (HR=1.89; 95% CI 1.28 to 2.77) and overall survival (OS) (HR=2.14; 95% CI 1.53 to 3.01). In subgroup analysis, IDC-P presence was significantly associated with poor PFS in prostate cancer treated by radical prostatectomy (RP) (HR = 2.48; 95% CI 2.05 to 3.00) and those by radiotherapy (RT) (HR=2.83; 95% CI 1.65 to 4.85). For clinicopathological characteristics, IDC-P present patients showed significantly higher tumor clinical stage, Gleason score and probability of lymph node invasive, positive surgical margin and positive extraprostatic extension.Conclusion Our meta-analysis indicates presence of IDC-P is closely correlated with poor prognosis and adverse clinicopathological characteristics. Our data support the value and clinical utility of routine detection of IDC-P by pathological examination. These conclusions need further validation and prospective studies are needed to find better treatment modalities for patients with IDC-P other than traditional first-line androgen deprivation therapy.

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The impact of intraductal carcinoma of the prostate on the site and timing of recurrence and cancer‐specific survival

Cited by 27 publications

References 27 publications

The influence of the presence of intraductal carcinoma of the prostate on the grade group system's prognostic performance

The influence of the presence of intraductal carcinoma of the prostate on the grade group system's prognostic performance

Intraductal carcinoma of the prostate in the absence of high‐grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations

The Presence of Intraductal Carcinoma of The Prostate Is Closely Correlated with Poor Prognosis: A Systematic Review and Meta-Analysis

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