Ductal carcinoma has been reported in approximately 0.2% of all prostate cancers. The common classic presentation is obstructive urinary symptoms or hematuria due to a prostatic urethral mass; however, ductal carcinoma may also arise in the peripheral or secondary periurethral ducts, either alone or in conjunction with acinar adenocarcinoma. This histological type was initially described as arising from the verumontanum. Architecturally, the cells are similar to endometrioid cancer, which gave rise to the hypothesis that the cells of origin were of remnant embryological origin. The term ‘Endometrioid’ carcinoma was used until ultra-structure studies revealed both light nonciliated cells and dark ciliated cells within 1 acinus.3
These same investigators also found strong staining for acid phosphatase. The cell of origin is now thought to be prostatic.3
Primary and metastatic ductal carcinoma stains for PSA and/or prostatic acid phosphatase in almost 100% of cases.4–8
Mixed acinar and ductal carcinomas occur in 48% to 87% of cases4,7,9,10
and may be in distinct components or merged. When diagnosed by needle biopsy, over 50% of the patients will have high-volume disease.9
PSA is expressed by ductal carcinoma cells, but is not elevated in all patients. The possibility of PSA production in an associated acinar component also makes interpretation of the PSA difficult and, as such, a normal serum PSA before surgery does not allow prediction of the final pathological stage.9
PSA cannot be reliably used to risk-stratify patients.
Christensen et al.10
reported a detailed account of 15 patients treated initially by radical prostatectomy. The mean age was 63 years and 9 of the 15 patients presented with obstructive urinary symptoms. Although before surgery all of the patients appeared to have resectable disease, the final pathology revealed extracapsular extension in 93% and positive margins in 47%. Pelvic lymph nodes were pathologically positive in 27% and seminal vesicle invasion was found in 40% of the patients. The resected tumors were large, with a mean volume of 8.4 cc and involved a mean of 23% of the prostate. Another series from Johns Hopkins reported outcomes of 58 patients diagnosed by needle biopsy, of which 20 were treated by radical prostatectomy.9
Similar to the previous experience, the extent of the tumors was clinically underappreciated and pathologically 65% had T3 disease, including 2 patients with seminal vesicle involvement. In this series >3 positive cores preoperatively were predictive of positive margins.
Although a number of patients with ductal carcinoma have been treated with RT, there have been no previous reports on doses or response rates. The important observation from our series was the long-term disease control achieved in 5 of the 6 patients, with 4 patients still alive and 3 patients disease-free between 3.6 and 4.8 years. Patient 2 was an outlier, who rapidly developed bony and visceral metastases and died 1.4 years from diagnosis with an undetectable PSA. In all of the patients treated with definitive RT pelvic lymph nodes were included in the initial treatment volume. In no patient was a local recurrence detected. The benefit of hormonal deprivation cannot be gauged from our series, but the addition of androgen deprivation was recommended for all the patients after 1992 (Patient 1). Patient 6 was treated 3 years after radical prostatectomy. On review of this case it is likely that metastatic disease was present before salvage therapy, as the PSA remained elevated despite removal of the recurrent urethral mass. Although not a curative treatment, RT in the setting of gross local recurrence appears to be of benefit for local control.
The natural history of ductal carcinoma is conflicting. Initial reports were of an indolent tumor that in some instances was observed for many years without reported clinical progression.1,11
More recent series have questioned this, reporting ductal carcinoma to commonly behave in an aggressive fashion, with a poor outcome.4,5,9,10
The exact role of hormonal deprivation is unknown. Initially the hypothesis of endometrial origin led clinicians to not utilize androgen deprivation in fear of stimulating the tumor growth.12
Case reports of patients responding to antiandrogen therapy were subsequently described.5,7
These findings combined with evidence that the ductal carcinoma cells are of prostatic origin has given rise to the routine use of androgen deprivation. An analysis of the hormonal expression of ductal carcinomas from 12 patients showed estrogen receptor reactivity in none of the 12, with positive staining for androgen receptors in 10 of the patients.8
The overall response to androgen deprivation is not as predictable as acinar carcinoma and some tumors will show no response.
Ductal carcinoma of the prostate has been reported to metastasize to lymph nodes and bone, similar to acinar carcinoma,4,5
although 2 series have highlighted a more unusual pattern of spread including 8 patients with liver metastases6
and 7 patients with metastases to the testicle or penis.13
Patient 5 in our series displayed a remarkable history, presenting with synchronous renal cell cancer and metastatic ductal carcinoma to the lung. After resection of the 2 lung metastases, RT to the prostate, and hormonal deprivation the patient is currently disease-free 4.2 years after the resection of his lung metastases. Patients with pulmonary metastases from ductal carcinoma have been reported previously. Millar et al.7
described a 74-year-old man who developed pulmonary metastases 2 years after a diagnosis of a papillary ductal carcinoma of the verumontanum. There was a response to androgen deprivation and the patient was alive at 11 years from diagnosis. Gong et al.6
reported on 23 patients with metastatic ductal carcinoma, which included 3 patients with pulmonary metastases. Two of these patients remained alive 21 months and 3 months after diagnosis, whereas the third patient died 46 months after diagnosis of his metastatic disease.
Ductal carcinoma of the prostate may be present as a urethral mass or within the prostate and at diagnosis both a cystoscopy and a TRUS prostate biopsy should be obtained if possible. If a urethral mass is present, maximum transurethral resection is indicated before RT Staging with whole-body bone scan and CT of the chest, abdomen, and pelvis should be performed in all patients. On biopsy, if >3 cores are positive there is a high likelihood of extracapsular extension and positive margins. Due to the possible extensive nature of the local disease, postoperative RT may be required after radical prostatectomy. Because the extent of disease is often underappreciated and PSA levels may not be representative, caution should be used in extrapolating risk models used in acinar carcinoma to make recommendations regarding surgery or definitive RT. As ductal carcinomas are often mixed with an acinar component, are usually bulky, histologically are considered high grade, and may respond to androgen deprivation, we recommend aggressive treatment. Our approach is to administer definitive prostate doses in the 80 Gy range, treatment of the pelvic lymph nodes, and 2–3 years of androgen deprivation in all patients irrespective of iPSA or clinical T-stage. Despite the presence of visceral metastatic disease, long-term disease-free intervals are possible and aggressive local treatment should be considered.