Treatment options for prostate adenocarcinoma
A 71-year-old Spanish man, who initially presented in 2003 with urinary hesitancy and frequency, was found to have a PSA of 13. A prostate biopsy showed adenocarcinoma in 5/6 cores with Gleason score of 4+4 involving left-sided seminal vesicle. A pelvic CT scan showed multiple enlarged illiac lymph nodes. The bone scan was negative for metastatic disease.
The patient was started on androgen deprivation therapy with leuprolide acetate and achieved a transient fall in his PSA levels. PSA remained stable for only one year and the level went up to 25 with the development of urinary obstruction secondary to involvement of the bladder neck. Bicalutamide (Casodex, AstraZeneca) was added and he was referred for local radiation to alleviate his symptoms. His PSA dropped again to 10 and disease remained in remission for another eight months.
In mid-2005 he presented to the emergency department with cough and shortness of breath. A chest X-ray showed multiple bilateral pulmonary masses. A subsequent chest, abdomen and pelvic CT scan showed bilateral lung masses and 3 cm to 4 cm liver masses involving both lobes along with enlarged prostate and pelvic lymph nodes. The bone scan was normal.
A biopsy of liver mass was conducted that showed prostate adenocarcinoma. His performance status remained reasonably good, so bicalutamide was discontinued and he was started on taxotere/prednisone along with leuprolide acetate shots. After two cycles of chemotherapy, he presented to his urologist with symptoms of urinary obstruction and was found to have clinical and serological progression of disease. The patient underwent transuretheral resection of prostate cancer and pathology showed invasive neuroendocrine carcinoma of prostate with positive immunohistochemistry of PSA, prostatic alkaline phosphatase and chromogranin A.
What will you do next?
A) Hormonal therapy with ketoconazole/hydrocortisone.
B) Change chemotherapy to another taxane.
C) Chemotherapy with platinum/etoposide.
D) Best supportive care.
Wajeeha Razaq, MD, is an Assistant Professor of Clinical Medicine in the Department of Internal Medicine, Section of Hematology/Oncology at the University of Nebraska and is also a member of the HemOnc Today Editorial Board.
Prostate cancer is the most commonly diagnosed cancer in American men except for nonmelanoma skin cancer. It has been detected with increasing frequency with the availability of serum PSA.
The adult prostate gland contains three types of epithelial cells: 1) secretary 2) basal and 3) neuroendocrine. Secretary cells are the most commonly encountered cells that require androgens for their growth and survival. Adenocarcinoma of prostate shows features common to this cell type. Basal cells are the primary epithelial cells and are androgen insensitive. Neuroendocrine cells are the endocrine and sensory cells similar to the neurons found in the prostate gland. Pure neuroendocrine carcinoma of prostate or small cell carcinoma is very rare (<1%), but is very aggressive (35% overall survival in two years; J Clin Oncol. 2002;20:30723080). It usually involves young men aged between 40 and 60 years and progresses rapidly.
Patients usually present with local symptoms like urinary obstruction and hematuria secondary to the involvement of bladder, seminal vesicles and ureters. Brain metastasis is very rare in prostate adenocarcinoma, but is more commonly seen in small cell prostate cancer. Tumor staging for prostate cancer with neuroendocrine differentiation is the same as used for prostate adenocarcinoma.
Cases with early stage disease are rare and patients usually present with either locally advanced or distant disease. Tumor markers are not helpful in this disease and PSA level, unlike prostate adenocarcinoma, does not co-relate with the disease progression. Chromogranin A is usually elevated in small cell carcinomas and carcinoids and may be followed during the course of treatment. Elevated CEA levels have also been reported in the literature.
Chemotherapy options for metastatic small cell prostate cancer are limited and an optimal regimen has not been established. Most often, cisplatin and etoposide have been tried with good clinical response.
In one series of 30 patients with prostate small cell carcinoma either detected by morphology or immunohistochemistry, patients were treated with cisplatin or carboplatin and etoposide and estramustine. Forty-four percent of patients with pure small cell histology, 46% with poorly differentiated cancer and 54% with one neuroendocrine marker immunohistochemically detected, had partial response (Acta Oncol. 2002;41:668-674). This study elaborated that a response was achieved with chemotherapy in these patients irrespective of the extent of the neuroendocrine differentiation. Modern chemotherapy agents like docetaxel along with cipslatin were also tried that showed an objective response of 41% with a median survival of 12 months (J Urol. 2007;178:844-848).
To achieve a higher response a three-drug regimen was also tried. A study from M.D. Anderson showed 61% objective response rate when infusional adriamycin was added to cisplatin and etosposide. But the median survival was only 10 months and there were three toxic deaths reported (J Clin Oncol. 2002;20:3072-3080).
We also treated our patient with cisplatin and etoposide. He had a good clinical response with decrease in chromogranin A levels for only three months. Eventually, he had radiological and clinical progression of disease and severe decline in his performance status. He was offered best supportive care at that time and died within a couple of weeks.