Historically, ductal PCa was thought to be less aggressive than adenocarcinoma;2, 7, 14
however, current evidence suggests that these patients are at an increased risk of disease progression.10–13
A number of findings in this study support the hypothesis that ductal carcinoma is an aggressive PCa subtype. First, ductal adenocarcinomas were significantly more likely to be poorly differentiated and have metastatic diseases than acinar adenocarcinomas. Second, in the subset of patients undergoing RP — and therefore with complete pathologic information — both grade and stage were significantly higher in those with ductal cancer. Third, patients with localized or regional ductal cancer had a greater than two-fold increased risk of PCSM compared to patients with acinar carcinoma after adjusting for relevant clinical and pathologic variables. These findings suggest that the detection of ductal carcinoma on pathology independently predicts a worse overall prognosis.
A potentially important finding is the apparent decreased PSA secretion of ductal carcinomas. Evidence for decreased secretion of PSA by ductal prostate cancers has been reported in smaller series. In a study of 46 patients with metastatic prostate cancer and a PSA ≤ 2 ng/ml, 9 (20%) were found to have ductal histology — a much higher percentage than would be expected based on the incidence of ductal cancer.15
Additionally, progression of disease in a patient with ductal cancer with no evidence of biochemical recurrence was also observed in another small institutional cohort.16
Although our study could not assess PSA recurrences after primary therapy, we were able to explore PSA levels at presentation. After adjusting for relevant clinical and pathologic factors including stage and grade, the mean PSA levels were 30% lower in patients with ductal cancer. While others have found similar PSA levels between ductal and acinar cases,17
no prior study has assessed PSA expression within a multivariate analysis. We also assessed the likelihood of patients with ductal cancers having a PSA <4.0 ng/ml, a commonly used cut-point in determining whether or not a prostate needle biopsy should be performed. In the multivariable analysis, patients with ductal carcinoma were 2.4 times more likely to have a PSA below 4.0 ng/ml, suggesting these cancers are less likely to be detected by PSA screening than acinar adenocarcinomas. This difference in serum PSA could be related to some ductal cancers being identified during endoscopic resection of a urethral polyp, but it may also be due to the pattern of tumor growth within the prostatic ducts leading to a relative increase in luminal PSA secretion and decrease in serum PSA secretion. Additionally, while PSA expression itself may be reduced in ductal tumors, further studies are necessary to assess this hypothesis. The decreased likelihood of identifying these tumors by PSA screening may play a role in the increased aggressiveness of ductal cancers due to a delay in diagnosis.
The unique attributes of ductal prostate cancer have been demonstrated in multiple studies. Unlike acinar adenocarcinoma, ductal cancers may present as a urethral polyp and are sometimes diagnosed on transurethral biopsy.4, 18, 19
However, ductal cancers diagnosed on urethral biopsy are only rarely confined to the urethra.18
Additionally, cancers with ductal histology are generally found to have an acinar component as well.3, 5
In a recently published study, Tu etal.20
showed that, in their cohort of patients, there was a correlation between the composition of the ductal carcinoma (pure versus mixed) and the overall mortality and risk of metastasis. The mixed ductal prostate cancers appeared to be associated with an increased risk of metastasis and increased overall mortality compared with pure ductal carcinomas. They reported a median 8.9 year overall survival in their cohort of 50 patients who underwent surgery for mixed ductal carcinoma versus
13.8 years in 25 patients with pure ductal histology. The presence of any amount of ductal histology has also been found to be a predictor of extraprostatic extension at radical prostatectomy.17
Unlike acinar carcinoma, ductal cancers often spread to visceral organs such as the lungs and liver, and a number of patients with testicular or penile metastases have been reported.8, 16, 21, 22
There are a number of limitations to this study. First, although overall case ascertainment is near 100% in SEER, misclassified or missing data points introduce unmeasured bias. For example, SEER does not differentiate between mixed and pure ductal carcinoma, and therefore we were not able to separate these two entities. Central review of pathology was not possible and variation in pathologic interpretation may have introduced misclassification bias. It is also possible that ductal cancers were underreported in the SEER database, with some of the mixed ductal carcinomas being miscategorized as acinar adenocarcinomas. Second, comorbidity and secondary treatment data are not available. Third, tumor grade is reported as well, moderately, and poorly differentiated, limiting evaluation of histologic grade across the entire study cohort. However, analysis of patients with complete Gleason grade information — those diagnosed from 2004–2006 — showed that both grade and stage were higher in ductal relative to acinar tumors. Likely due to an insufficient number of events, no difference in PCSM was observed in this subgroup. Finally, as a retrospective study, there may have been unrecognized differences between the ductal and acinar groups for which we were unable to control.