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Journal of Clinical Oncology, Vol 26, No 7 (March 1), 2008: pp. 1168-1171 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.14.5409
Small-Cell Carcinoma of the ProstateDepartment of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT
Division of Urology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT
Department of Pathology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT
Department of Medicine, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT
Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT A 72-year-old man with a 3-year history of obstructive urinary symptoms presented with painless hematuria. On examination, induration was noted along the right lobe of the prostate with a large, firm, irregular mass extending superiorly off the right base of the gland. His prostate-specific antigen (PSA) was 1.6 ng/mL, and a comprehensive metabolic panel and CBC were within normal limits. Transrectal ultrasound-guided biopsy revealed a mixed histology of adenocarcinoma, Gleason grade 4+5, and small-cell carcinoma. A bone scan was normal and abdominopelvic computed tomography (CT) showed a large mass arising from the right base of the prostate and a right internal iliac node suspicious for cancer involvement. He was given a single 3-month injection of leuprolide and referred to the Huntsman Cancer Center at the University of Utah (Salt Lake City, UT), where the pathologic diagnosis was confirmed. Four of six core needle biopsies showed a homogeneous population of blue cells with round nuclei and a salt-and-pepper chromatin pattern consistent with small-cell carcinoma of the prostate (Fig 1A). Gleason 4+5 adenocarcinoma with perineural invasion was found adjacent to areas of small-cell carcinoma invading into adipose tissue (Fig 1B). Immunohistochemical staining for cell adhesion molecule 5.2, which identifies cells of epithelial origin, was diffusely positive for both carcinomas. Staining for CD45, the leukocyte common antigen, was negative for all cells, thus ruling out lymphoma. Additional immunohistochemical staining was not done because of the distinct morphology of the small-cell component. Whole-body [18F]fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) revealed a 7-cm mass extending from the superolateral margin of the prostate, with an elevated standard uptake value of 9.2 (Figs 2A to 2C: small arrow indicates the prostate mass). A second mass located superiorly at the right pelvic sidewall abutted the right ureter without evidence of obstruction (Figs 2B and 2D: large arrow indicates the pelvic sidewall mass; arrowhead indicates the ureter). A 1.5-cm lymph node with a standard uptake value of 2.2 was also seen adjacent to the right acetabulum. The prostate itself did not have abnormal uptake of FDG. Multidisciplinary consultation with urology, medical oncology, and radiation oncology led to a treatment recommendation of continued antiandrogen therapy, systemic chemotherapy, and radiation therapy to the patient's known sites of pelvic disease. Although chemotherapy was recommended strongly and frequently, the patient opted for treatment with radiation alone. Just before beginning radiotherapy, he developed right-sided abdominal pain and hydronephrosis, which required ureteral stenting. He then started radiation receiving 50.4 Gy to a pelvic field encompassing known disease and the nodal drainage (Fig 3). An additional 9 Gy was administered to the right pelvic mass and prostate, and then an additional 12.6 Gy intensity-modulated radiation therapy boost was administered to the prostatic mass for a total dose of 72 Gy. A CT of the abdomen and pelvis obtained in follow-up 2 months after completion of radiotherapy revealed near-complete resolution of the large pelvic mass. However, a small aorto-caval lymph node was now visible. In addition, the patient complained of diffuse bone pain. PET/CT showed diffuse disease throughout the entire axillary and appendicular skeleton, except where he had been irradiated. There was marked decrease in size of both the prostatic mass and the right pelvic side wall mass, and they were no longer PET avid (Fig 4A: small arrows indicate inferior extent of boney disease; large arrow indicates new para-aortic node; arrowhead indicates bowel). Short-tau inversion recovery magnetic resonance imaging of the lumbar spine showed diffuse vertebral metastases extending superiorly starting at L4 (Fig 4B). Overlay of the radiation isodose lines onto the post-treatment CT scan indicated diffuse osseous metastases beginning just superior to the pelvic field (not shown). The patient again refused chemotherapy and received palliative radiotherapy to painful boney metastases. He died as a result of his disease 1 month later, 6 months after the date of his initial diagnosis.
Most patients with small-cell carcinoma of the prostate are symptomatic at diagnosis, unlike patients with prostate adenocarcinoma alone. Signs and symptoms, in order of frequency, include obstructive, neurologic, and constitutional symptoms, followed by symptoms from paraneoplastic syndromes, bone pain, hydronephrosis, abdominal pain, hematochezia, and hematuria.1 Clinical features of small-cell carcinoma of the prostate include a markedly enlarged prostate, disproportionately low PSA levels in the presence of metastatic disease, unresponsiveness to hormone therapy, visceral metastases, and high proportion of lytic to blastic bone lesions.2-4 The identification of prostatic tumors with a neuroendocrine component has increased steadily from 10% in the 1970s to as high as 100%, as found by Abrahamsson et al in 1987, due to improved assays. These tests include more sensitive silver stains, the use of newly developed immunocytochemical analyses, and the use of antibodies to specific neuroendocrine peptides and serotonin.5-11 Neuroendocrine cells range from the focal neuroendocrine differentiation commonly observed in conventional prostatic adenocarcinoma to rarer entities such as small-cell carcinoma, carcinoid-like tumors, and Paneth-like cells.12,13 Small-cell carcinoma of the prostate accounts for 0.5% to 2% of all prostatic malignancies.14,15 Adenocarcinoma elements are present concomitantly in approximately 50% of cases, but prognosis does not appear to be affected by the presence of a non–small-cell component.2,3 Histologic features include sheets of small round blue cells with a high nuclear-to-cytoplasmic ratio, necrosis, coarse (salt and pepper) chromatin, and nuclear molding. Small-cell carcinoma of the prostate usually stains positive for neuron-specific enolase, synaptophysin, and chromogranin A, and negative for androgen receptor and PSA.14 Although PET imaging has been shown to be useful for staging small-cell lung cancer,16,17 the rarity of small-cell prostate cancer has precluded a similar analysis. Carbon-11-labelled acetate has been shown to offer benefits in sensitivity over [18F]FDG for prostate adenocarcinoma, but this method is still investigational and there are significant limitations to the accuracy of these imaging studies.18-20 Therefore, although the small-cell component of our patient's cancer in the radiation field may have been eliminated, the PET/CT may not have detected the adenocarcinoma component or assessed its viability. Median survival time is poor for patients with small-cell carcinoma of the prostate, ranging from 5 to 17.5 months.2-4,14,21,22 Recommended treatment regimens for small-cell prostate cancer are similar to those for small-cell carcinoma of the lung. Chemotherapy is the mainstay of treatment,2-4,21,22 with radiation used to supplement local control or for palliation of symptoms in metastatic disease.3,4,21 Cisplatin and etoposide are the most commonly recommended agents, and a recent phase II trial showed the addition of doxorubicin to this regimen added to toxicity but not survival.22 For localized disease, surgery is often included, and it may even be curative.23 In fact, primary surgery was the only independent prognostic factor for prolonged survival in one relatively large retrospective univariate analysis of 60 patients.24 Because of the aggressive nature of small-cell carcinoma and the frequent simultaneous presence of high-grade adenocarcinoma, the addition of androgen suppression therapy is logical, although its exact benefits are undefined. Our patient's marked response to radiotherapy highlights the radiosensitivity of small-cell carcinoma of the prostate. The rapid progression to widespread metastatic disease outside the irradiated volume underscores the importance of chemotherapy in this frequently systemic disease. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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