Introduction:

Ductal Prostatic adenocarcinoma (DAC) is an aggressive histologic variant of prostate cancer (PCa) accounting for between 0.1-7% cases. DAC often presents as locally advanced or metastatic disease posing a significant challenge in management.

In this study, we aim to investigate the patterns of metastases in men presenting with DAC, in order to further characterize this condition.

Methods:

After obtaining IRB approval, the records of all patients referred to our institution with DAC from January 2005 to November 2018 were identified using natural language processing and electronic medical record verification. Patients with a new diagnosis of DAC with de novo metastatic disease, those with localized disease who developed metastases post-treatment and those who were free of disease post primary therapy were included. All patients had their pathology reviewed centrally at our institution to confirm the diagnosis. Patient data including age, tumor characteristics, presence of symptoms, PSA values, treatments, progression, sites and dates of metastases, and reported deaths were collected and analyzed.

Student T tests, Chi-squared analysis, Kruskal-Wallis test and Kaplan Meier analyses were performed to assess the baseline demographic and tumor characteristics.

Results:

423 men with a new diagnosis of DAC were included. 164 (38.8%) had metastatic DAC (mDAC); 112 had de novo metastases while the remainder (52) developed metastases post-treatment. Men with de novo metastases had higher median PSA (36.4 vs 6) and higher ISUP grade group 4/5 disease (98.2% vs 86.3%) but lower cT3/T4 stage (28.6% vs 60%), compared to those with metastases post primary treatment (all p <0.05) (Table 1).

Men with de novo mDAC and those who developed metastases post-treatment had multiple metastatic sites, commonly bone, lymph node and viscera, with higher rates of lung metastases seen in the post-treatment group (23.2% vs 44.2%, p=0.01) (Table 1). Eighty-seven percent of men with de novo metastases, required, on average, 3.2 lines of systemic treatment (range 1-11) and 37.6% required radiotherapy or surgical intervention for palliation of symptoms.

Of the patients who initially presented with localized disease, 259 were free of disease post primary therapy, while 52 progressed to metastases. Of the latter group, 46 were treated with curative intent (34 radical prostatectomy and 12 radiotherapy) but developed metastases at a median time of 22 months (range 0.9 – 74.8 months) post-treatment. In this group, the median PSA at the time of metastases was 4 ng/ml (range 0.2 to 184). Men with de novo metastases had a worse overall 5-year survival (26%) compared to those who progressed to metastases post-treatment for localized DAC (63%) and those who did not develop metastases (74%) (p<0.001) (Figure 1).

Conclusion:

This study describes the metastatic patterns of DAC. Despite aggressive therapy and palliation, DAC has a poor prognosis both in patients with de novo metastatic disease and those who later progress to metastases. Men who receive treatment for DAC with curative intent require stringent long-term follow up with imaging modalities including chest imaging given the predilection for lung metastases. The results from this study highlight the need for better understanding of the biology of DAC and the development of novel therapies.  

Funding: AUA Urology Care Foundation Research Scholar Award