BERKELEY, CA (UroToday.com) - In our recent article, we highlighted a case of small cell carcinoma. This type of prostate cancer grows more rapidly than the usual prostate adenocarcinoma and results in greater incidence of metastases. In addition, prostate specific antigen (PSA) levels in small cell carcinoma are likely to be normal, or slightly higher than normal, even when there is spread of cancer.
In our patient, the TRUS prostate biopsy result was adenocarcinoma, explaining the high levels of PSA initially, but the L5 lesion biopsy result was small cell neuroendocrine carcinoma. In small cell prostate carcinoma, other tumor markers are usually high, such as chromogranin A, serotonin, calcitonin and glucagon (1). These can be useful tools to monitor tumor recurrence. Small cell prostate carcinoma patients can have paraneoplastic syndrome which can cause symptoms differentiating them from the usual prostate adenocarcinoma. Other studies showed that half of the small cell prostate cancers have other types of cells mixed with the small cells, and this may explain the discordance between the prostate biopsy and the L5 lesion biopsy in our case.
After lymph nodes, the most common site of metastases in prostate adenocarcinoma is the bone, however, prostate small cell carcinoma usually metastasizes to other organs such as the lungs and liver (although it can spread to any part of the body). Small cell carcinoma usually invades outside the prostate -- commonly the surrounding organs, regional lymph nodes, and other distant organs in comparison to prostate adenocarcinoma.[1]
The bone lesions in our case were detected during an MRI scan for local staging of the prostate cancer. The appearance of suspicious hyper-enhancing lesions was very suggestive of bone metastases. Surprisingly, the fluorine-18 fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) scan, which would be expected to further highlight the bone lesions, was negative. Then, a technetium-99m methyl diphosphate (Tc99m-MDP) bone scan with additional single-photon emission computed tomography (SPECT)/CT imaging was done, and it turned out to be negative as well. So, to confirm the diagnosis of bone metastases in our case, we ended up performing a percutaneous core biopsy for one of the bone lesions which confirmed the diagnosis of bone metastases with histological features of small cell (neuroendocrine) variant of prostate cancer.
The dilemma of confirming the bone lesions as metastases, or due to other cause, is the issue in our case. The cell type of the metastases being small cell neuroendocrine prostate carcinoma further complicated the case and made the diagnosis of bone metastases difficult.
The knowledge of different types of tumors involved in the prostate gland facilitates the process of diagnosing tumors by different tracers which are specific for that tumor. Neuroendocrine tumors usually have somatostatin receptors which are avid for radiotracers having somatostatin analogs. In the literature, radiotracers, having more resolution and affinity for endocrine tumor receptors, are used and investigated in prostate carcinoma -- for example, in 111Octreoscan (somatostatin analogs) and Ga-68 labeled somatostatin analogs DOTA (TATE) or (NOC). Baum, et al. investigated more tracers such as Tc-99m demobesin which is a gastrin releasing peptide receptor antagonist (GRP), Ga-68 AMBA (DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2) which is a bombesin analogue- GRP, and NMB (neuromedin B) receptor targeting, Ga-68 demobesin, Ga-68 sarabesin-6 which is also a GRP antagonist.[2] In addition, other tracers for metastatic prostate adenocarcinoma are under investigation including 11C-acetate and 18F-fluoroacetate for lymph node metastases and 11C-acetate, 11C-methionine, and 18F-fluoride for bone metastases.[3]
Furthermore, being able to target the cell type in these cases opens the door for additional peptide receptor radionuclide therapy (PRRNT). Trials were done by Baum, et al. using Lu-177 sarabesin-6 in prostate carcinoma with widespread metastases.[2] Another way of treating this tumor is using both radiation and cytotoxic chemotherapy, which shows good response and palliation.[4] The role of PET/MRI in these cases could be an area of interest to researchers, for local staging as well as for distant metastases.
References:
- David G Wagner, MD; Liang Cheng, MD et al. Pathology of Small Cell Prostate Carcinoma. emedicine.medscape.com.
- Baum RP, Kulkarni HR. THERANOSTICS: From Molecular Imaging Using Ga-68 Labeled Tracers and PET/CT to Personalized Radionuclide Therapy - The Bad Berka Experience. Theranostics 2012; 2(5):437-447. doi:10.7150/thno.3645.
- Geert M Villeirs, MD, PhD; Eugene C Lin, MD et al. Imaging in Prostate Carcinoma. emedicine.medscape.com.
- C Nutting, A Horwich, C Fisher, C Parsons, and D P Dearnaley. Small-cell carcinoma of the prostate. J R Soc Med. 1997 June; 90(6): 340–341.
Written by:
Ammad Al Tamimi MD, FRCR as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Nuclear Medicine and PET, Singapore General Hospital, Singapore
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