The Clinical Impact of Comedonecrosis Within Intraductal Carcinoma of the Prostate

Abstract

Context.— Intraductal carcinoma of the prostate (IDC-P) is considered a distinct form of aggressive prostate cancer where comedonecrosis, a grade 5 pattern, is occasionally present. Meanwhile, assigning a Gleason grade to IDC-P remains controversial. Objective.— To assess the clinical significance of necrosis associated with IDC-P. Design.— We compared radical prostatectomy (RP) findings and oncologic outcomes in men with prostate cancer exhibiting IDC-P with (IDC-P+/N+) versus without (IDC-P+/N−) comedonecrosis. Results.— Of the 558 RPs examined, IDC-P was present in 213 cases (38.2%), including 167 (78.4%) with IDC-P+/N− and 46 (21.6%) with IDC-P+/N+. When comparing IDC-P+/N− versus IDC-P+/N+ cases, the presence of necrosis was significantly associated with higher tumor grade, higher incidence of pT3/pT3b or pN1 disease, and larger estimated tumor volume. Outcome analysis revealed a significantly higher risk of disease progression in IDC-P+/N+ patients than in IDC-P+/N− patients (P < .001). Significant differences in progression-free survival between IDC-P+/N− and IDC-P+/N+ patients were also seen in subgroups, such as those without (P = .01) or with (P = .03) adjuvant therapy immediately after RP, those with pN0 disease (P < .001), and, more interestingly, those exhibiting conventional Gleason pattern 5 component (P = .02). Multivariate analysis showed significance for IDC-P+/N+ when IDC-P (grade 4) and IDC-P+/N+ (grade 5) were (hazard ratio, 1.768; P = .049) or were not (hazard ratio, 2.000; P = .008) incorporated into the Gleason score. Conclusions.— IDC-P+/N+ was found to be associated with worse histopathologic features on RP and poorer prognosis as an independent predictor. Pathologists may thus need to report the presence or absence of not only IDC-P but also comedonecrosis within IDC-P.

Impact of comedonecrosis on prostate cancer outcome: a systematic review

“…The 2016 World Health Organisation (WHO), 2014 and 2019 ISUP recommendations were used in all manuscripts on acinar adenocarcinoma, one on ductal adenocarcinoma and one on intraductal carcinoma (n = 8). [14][15][16][17][18][19][20][21] The remaining four manuscripts used either Epstein's (n = 2) 22,23 or McNeal's (n = 1) 24 criteria for IDC, while one report on comedonecrosis in ductal adenocarcinoma 25 did not specify formal diagnostic criteria. One study explicitly provided a definition of comedonecrosis, i.e.…”

“…17 Ten studies explicitly stated they used whole slides for review. [14][15][16][17][18][19][22][23][24][25] In nine studies, slides were reviewed by at least one pathologist 14,15,[18][19][20][21][22][23][24] who was explicitly blinded for clinical outcome in seven studies. 14,[18][19][20][21][22]24 In total, 4059 patients were included in the 12 studies, 410 of whom were reported to have comedonecrosis (Table 1).…”

“…Six reports focused upon comedonecrosis in acinar adenocarcinoma, four in IDC and two in ductal carcinoma. Biochemical recurrence (BCR) was included as an endpoint in 10 manuscripts and was defined as two consecutive postoperative serum prostate-specific antigen (PSA) values of ≥ 0.2 ng/ml, 18,20,25 one postoperative PSA level ≥ 0.2 ng/ml, [14][15][16][17]21,22 and one postoperative PSA ≥ 0.4 ng/ml. 24 Metastasis-free survival, 18 PCaspecific mortality, 19 overall and castration-resistant PCa-free survival 23 were each investigated by one study.…”

“…15,17,21,24 Median time of follow-up was ≥ 12 months for eight studies and not specifically recorded for the other four. 14,18,19,21…”

“…Wang et al 21 included 558 grade group > 1 radical prostatectomy specimen, 213 of which had IDC (38%), and investigated the impact of comedonecrosis (46 of 213, 22%) in IDC. Men with IDC with comedonecrosis more frequently had grade group ≥ 3 (P < 0.001), pT3 stage (P = 0.009), higher tumour volume (P < 0.001) and lymph node metastasis (P = 0.02) at time of operation than IDC cases without comedonecrosis.…”