Ductal Prostate Cancers Demonstrate Poor Outcomes with Conventional Therapies

Ranasinghe, Weranja; Shapiro, Daniel D.; Hwang, Hyunsoo; Wang, Xuemei; Reichard, Chad A.; Elsheshtawi, Mohamed A; Achim, Mary; Bathala, Tharakeswara K.; Tang, Chad; Aparicio, Ana; Tu, Shi Ming; Navone, Nora M.; Thompson, Timothy C.; Pisters, Louis L.; Troncoso, Patricia; Davis, John W.; Chapin, Brian F.

doi:10.1016/j.eururo.2020.11.015

Cited by 30 publications

(29 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whole genome doubling/ploidy increase is arguably the genomic feature most strongly associated with advanced prostate cancer 27 . These findings are in accordance with earlier clinical descriptions of DA as an aggressive neoplasm 7 …”

Section: Discussionsupporting

confidence: 89%

See 1 more Smart Citation

Ductal and acinar components of mixed prostatic adenocarcinoma frequently have a common clonal origin

et al. 2022

View full text Add to dashboard Cite

Background Ductal adenocarcinoma (DA) is an aggressive subtype of prostate cancer. It is most commonly seen in mixed tumors together with conventional acinar adenocarcinoma (AA). The genetic profile of DA and its clonal origin is not fully characterized. Objective To investigate whether DA represents a distinct genetic subtype and to investigate the somatic relationship between the ductal and acinar components of mixed cancers. Design, Setting, and Participants In 17 radical prostatectomy specimens ductal and acinar tumor components from the same tumor foci were dissected. DNA was extracted and genomic sequencing performed. After exclusion of two cases with low cell yield, 15 paired samples remained for analysis. Results In 12 of 15 cases a common somatic denominator was identified, while three cases had clonally separate components. In DA, TMPRSS2‐ERG gene fusions were detected in 47% (7/15), clonal FOXA1 alterations in 33% (5/15) and SPOP alterations in 27% (4/15) of cases. In one case KIAA1549−BRAF fusion was identified. Genome doubling events, resulting in an increased ploidy, were identified in the DA in 53% (8/15) of cases, but not seen in any AA. PTEN and CTNNB1 alterations were enriched in DA (6/15) but not seen in any AA. No cancers showed microsatellite instability or high tumor mutation burden. Conclusions Ductal and acinar prostate adenocarcinoma components of mixed tumors most often share the same origin and are clonally related. DA components in mixed tumor often exhibit genome doubling events resulting in aneuploidy, consistent with the aggressive nature of high grade prostate cancer.

show abstract

Section: Discussionsupporting

confidence: 89%

“…In the absence of necrosis, DA without an AA component is, by definition, assigned a Gleason score of 4 + 4 = 8 (ISUP Grade 4), as its clinical behavior has been shown to be similar to that of AAs of this grade 6 . DA is reported to have a less favorable prognosis than AA following radical prostatectomy or radiotherapy 7 …”

Section: Introductionmentioning

confidence: 99%

Ductal and acinar components of mixed prostatic adenocarcinoma frequently have a common clonal origin

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Metastasis-free survival of pure PDA was described as worse compared with mixed acinar and ductal cancer, as well as pure acinar cancer. Ranasinghe et al 38 grouped pT3 and pT4 cases as well as GG4 and GG5 cancers for analysis, which may explain some of the differences observed between their study and our findings. Furthermore, data regarding specimen processing (ie, entire or partial gland submission for histologic examination) and grading (ie, global grading versus grading of individual TNs) were not provided for comparison and may also influence reported outcomes.…”

Section: Discussioncontrasting

confidence: 73%

“…Ranasinghe et al 38 recently conducted a single-center retrospective review of 163 men with PDA and 155 men with high-risk classic PAA treated with RP. The authors reported no difference in the incidence of BCR between PDA and acinar cancers (77 of 163 versus 57 of 155; P ¼ .069).…”

Section: Discussionmentioning

confidence: 99%

Prostatic Ductal Adenocarcinoma Controlled for Tumor Grade, Stage, and Margin Status Does Not Independently Influence the Likelihood of Biochemical Recurrence in Localized Prostate Cancer After Radical Prostatectomy

Kryvenko

Iakymenko

Guido

et al. 2021

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

Context.— Prostatic ductal adenocarcinoma (PDA) has historically been considered to be an aggressive subtype of prostate cancer. Objective.— To investigate if PDA is independently associated with worse biochemical recurrence (BCR)–free survival after radical prostatectomy. Design.— A review of 1584 radical prostatectomies was performed to grade, stage, and assess margin status in each tumor nodule. Radical prostatectomies with localized PDA (ie, those lacking metastasis) in the tumor nodule with the highest grade and stage and worst margin status were matched with prostatic acinar adenocarcinoma according to grade, stage, and margin status. The effect of PDA on BCR was assessed by multivariable Cox regression and Kaplan-Meier analyses. Results.— Prostatic ductal adenocarcinoma was present in 171 cases. We excluded 24 cases because of lymph node metastasis (n = 13), PDA not in the highest-grade tumor nodule (n = 9), and positive surgical margin in a lower-grade tumor nodule (n = 2). The remaining 147 cases included 26 Grade Group (GG) 2, 44 GG3, 6 GG4, and 71 GG5 cancers. Seventy-six cases had extraprostatic extension, 33 had seminal vesicle invasion, and 65 had positive margins. Follow-up was available for 113 PDA and 109 prostatic acinar adenocarcinoma cases. Prostate-specific antigen density (odds ratio, 3.7; P = .001), cancer grade (odds ratio, 3.3–4.3; P = .02), positive surgical margin (odds ratio, 1.7; P = .02), and tumor volume (odds ratio, 1.3; P = .02) were associated with BCR in multivariable analysis. Prostatic ductal adenocarcinoma, its percentage, intraductal carcinoma, and cribriform Gleason pattern 4 were not significant independent predictors of BCR. Conclusions.— Advanced locoregional stage, higher tumor grade, and positive surgical margin status rather than the mere presence of PDA are more predictive of worse BCR-free survival outcomes following radical prostatectomy in men with a component of PDA.

show abstract

“…Clinically, ductal carcinoma is associated with worse pathologic parameters [89] and is an independent indicator of worse biochemical-free [90,91], metastasis-free [92] and overall survival [93] compared to acinar carcinoma. Morphologically, ductal carcinoma may have various patterns, usually more than one within the same case, the most characteristic being a papillary pattern with true fibrovascular cores lined by tall pseudostratified columnar cells (Figure 5) [94].…”

Section: Ductal Carcinomamentioning

confidence: 99%

Cribriform Patterned Lesions in the Prostate Gland with Emphasis on Differential Diagnosis and Clinical Significance

Destouni

Lazaris

Tzelepi

2022

Cancers

View full text Add to dashboard Cite

Cribriform glandular formations are characterized by a continuous proliferation of cells with intermingled lumina and can constitute a major or minor part of physiologic (normal central zone glands), benign (clear cell cribriform hyperplasia and basal cell hyperplasia), premalignant (high-grade prostatic intraepithelial neoplasia), borderline (atypical intraductal cribriform proliferation) or clearly malignant (intraductal, acinar, ductal and basal cell carcinoma) lesions. Each displays a different clinical course and variability in clinical management and prognosis. The aim of this review is to summarize the current knowledge regarding the morphological features, differential diagnosis, molecular profile and clinical significance of the cribriform-patterned entities of the prostate gland. Areas of controversy regarding their management, i.e., the grading of Intaductal Carcinoma, will also be discussed. Understanding the distinct nature of each cribriform lesion leads to the correct diagnosis and ensures accuracy in clinical decision-making, prognosis prediction and personalized risk stratification of patients.

show abstract

Ductal Prostate Cancers Demonstrate Poor Outcomes with Conventional Therapies

Cited by 30 publications

References 26 publications

Ductal and acinar components of mixed prostatic adenocarcinoma frequently have a common clonal origin

Ductal and acinar components of mixed prostatic adenocarcinoma frequently have a common clonal origin

Prostatic Ductal Adenocarcinoma Controlled for Tumor Grade, Stage, and Margin Status Does Not Independently Influence the Likelihood of Biochemical Recurrence in Localized Prostate Cancer After Radical Prostatectomy

Cribriform Patterned Lesions in the Prostate Gland with Emphasis on Differential Diagnosis and Clinical Significance

Contact Info

Product

Resources

About