Inadequate Grading of Intraductal Carcinoma of the Prostate

BOSTON — Solid intraductal carcinoma of the prostate (IDC-P) is associated with significantly worse outcomes compared with conventional Gleason grade 5 prostate cancers and is more commonly present in metastatic than nonmetastatic cancers, according to two studies presented this week at the United States and Canadian Academy of Pathology (USCAP) 2025 Annual Meeting.

“Our findings suggest that solid IDC-P is more aggressive than Gleason grade 5 conventional prostate adenocarcinoma or cribriform IDC-P,” and it may therefore be better not to consider it as a grade 5 pattern, said first author of one of the studies, Hangchuan Shi, MD, PhD, of the University of Rochester Medical Center, in Rochester, New York.

Although IDC-P — reported in about 20% of men with prostate cancer — is known to be associated with poorer response to treatment, there is a debate over whether to grade the entity with Gleason scoring or not.

The International Society of Urological Pathology recommends incorporating IDC-P into the Gleason score, while the Genitourinary Pathology Society does not.

To evaluate the prognostic significance of solid IDC-P compared with Gleason grade 5 conventional prostate cancer, Shi and his colleagues identified 115 cases in the surgical pathology database at the University of Rochester Medical Center between 2008 and 2015 involving Gleason grade 5 conventional prostatic adenocarcinoma as a primary, secondary, or tertiary pattern, as well as cribriform IDC-P.

The researchers excluded cases showing comedonecrosis within IDC-P, due to the potential for worse outcomes.

Of the grade 5 conventional prostate cancer cases with cribriform carcinoma, 28 (24.3%) had solid nest pattern IDC-P. Patients with and without solid IDC-P had a matching mean age of about 64 years, and their mean preoperative PSA was about 12.27 ng/mL.

Adjuvant therapy prior to recurrence was significantly more common in those who had solid IDC-P (60.7% vs 34.5%; P = .016).

Compared with the conventional prostate cancer cases, those with solid IDC-P had a significantly higher incidence of lymph node metastasis (P = .014) and had larger estimated tumor volume (P = .011).

There were no significant differences in other clinicopathologic features, such as preoperative prostate-specific antigen, grade group, pT stage, and surgical margin status.

After adjustment for key factors in a multivariable analysis, solid IDC-P was significantly associated with poorer recurrence-free survival (P = .007), and poorer cancer-specific survival (P = .004).

Finally, solid IDC-P was an independent predictor of recurrence (hazard ratio [HR] 1.960; P = .031), whereas other measures, including prostate-specific antigen (PSA), cancer grade, pT, lymph node metastasis, surgical and tumor volume were not significant factors.

“We found the solid IDC-P patients had almost two-times the risk of recurrence compared with the patients without solid IDC-P in our study,” Shi said.

The findings underscore the importance of accurately identifying IDC-P, senior author Hiroshi Miyamoto, MD, PhD, director of Genitourinary Pathology at School of Medicine and Dentistry, University of Rochester, Rochester, New York, told Medscape Medical News.

“It may be difficult for some pathologists, especially those who have no specific training in genitourinary pathology, to adequately recognize” this form of cancer, he said.

Although it is recognized as an aggressive form of prostate cancer, “based on our studies, we believe that it is inadequate to grade IDC-P” as a Gleason grade 5 cancer, Miyamoto added.

IDC More Common in Metastases 

Poorer outcomes associated with IDC-P were further described in a post hoc sub-analysis of the phase 3, prospective PATRON clinical trial that is evaluating prostate-specific membrane antigen (PSMA) PET-CT–guided intensification of therapy.

In the multicenter trial, 825 patients were stratified into three cohorts: High-risk patients receiving radiation therapy (45%), high-risk patients receiving salvage radiation therapy post-radical prostatectomy (47%), and those receiving a radical prostatectomy (8%).

The patients in all three cohorts were randomized 1:1 to receive imaging with or without PSMA PET-CT.

IDC-P and/or cribriform carcinoma were present among 342 patients in the PSMA PET-CT group including 48% of high-risk patients receiving radiotherapy, 42% of high-risk patients receiving salvage radiation therapy post-radical prostatectomy, and 40% of those receiving a radical prostatectomy.

IDC-P was reported in 64% of cases with metastases detected by PSMA PET-CT compared with just 36% of cases without metastasis (P = .008), with the ratios being similar in each individual patient cohort.

Of note, the association between the presence of IDC-P and metastases was not observed when IDC-P and cribriform carcinoma were combined — IDC-P and/or cribriform carcinoma was detected in 54% of cases with PSMA PET-CT–detectable metastasis and in 46% of cases without metastasis (P = .362).

The first author Dominique Trudel, MD, PhD, of the Centre Hospitalier de l’Université de Montréal, Montreal, Quebec, Canada, said the findings add to understanding of IDC-P’s relationship with poorer outcomes.

“As pathologists, we know that IDC is associated with poor outcomes and that men with IDC who are treated with standard therapies do benefit from them, but they never benefit as much as men without IDC,” she told Medscape Medical News.

As the study is ongoing, “in approximately 4-5 years, we will know how much of a difference IDC-P makes in outcomes after treatment,” Trudel noted.

The take-home message from the collective research should be that “IDC-P matters,” she said.

“I think that if your patient has IDC-P and [cribriform carcinoma], it is worth at least asking someone from an academic center to see what the treatment options are. We know that some radiation oncologists are increasing doses for IDC-P. It is empiric, but they’re doing it,” she explained.

The authors had no disclosures to report.