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Page 2 of 8 Fiordoliva et al. J Cancer Metastasis Treat 2019;5:59 I http://dx.doi.org/10.20517/2394-4722.2019.23

of neuroendocrine (NE) tumors of prostatic adenocarcinoma (PAC) includes the following four
categories: Adenocarcinoma with neuroendocrine differentiation, Well-differentiated NE tumor
(carcinoid tumor), Small cell NE carcinoma and Large cell NE carcinoma. Gleason score and grade
group are the standard approach to histologic grading of PAC, but not for the NE components, and
[2,3]
it is an important independent prognostic factor . Clinical presentation and prognosis usually
depend on local infiltration and metastatic spread. Paraneoplastic syndromes including syndrome
of inappropriate antidiuresis (SIAD) are rare, mostly in poorly differentiated PAC, frequently with
[4]
NE features . SIAD is commonly associated with small cell lung cancer (SCLC), non-small cell
[5]
lung cancer (NSCLC), gastrointestinal cancers, kidney cancers and mesothelioma . In the last few
years, several international and national guidelines have been published in order to improve clinical
[6]
managing of this electrolyte disorder . Oral tolvaptan, a vasopressin-2-receptor antagonist, has been
approved by FDA and EMA for treatment of euvolemic hyponatremia due to SIAD with mild or
moderate symptoms. Vaptans demonstrated to improve serum sodium concentration in patients with
[7]
SIAD but there are still few data about their possible effect on survival of cancer patients .

CASE REPORT
A 60-year-old male with PAC and abdominal lymph nodes and axial bone metastasis came to our
Department. An informed consent to procedures and therapy was obtained from the patient. At first
observation, the patient was in good clinical condition (Performance status according to Eastern
Cooperative Oncology Group-ECOG-PS = 0) and he did not present significant comorbidities other
than well-controlled arterial hypertension.

PAC diagnosis occurred in June 2014 when, after onset of urinary frequency and dysuria, patient
underwent prostate biopsies. Histological examination reported prostatic acinar adenocarcinoma
Gleason score 5 + 4 = 9 (grade group 5, with NE differentiation = 5%) [Figure 1]. PSA was 22 ng/mL.

After diagnosis, a CT scan showed left iliac chain, para-aortic and inguinal bilateral lympha-
denomegalies and osteoblastic metastasis to lumbar spin, multiple ribs and hip with no fracture risk.
A bone scintigraphy confirmed bone involvement [Figure 2]. Laboratory values did not show clinically
significant abnormalities.

In August 2014 the patient started complete androgen deprivation therapy with oral Bicalutamide
50 mg daily along with intramuscular Leuprorelin 11.25 mg/mL quarterly. Denosumab 120 mg
monthly was started to prevent skeletal events. Serum PSA showed initial complete biochemical
response (0.3 ng/mL). In November 2014 PSA raised to 10 ng/mL. The patient presented with clinical
worsening including increased urinary frequency and dysuria. Considering biochemical and clinical
2
progression, Bicalutamide was stopped and first-line chemotherapy with Docetaxel 75 mg/m
intravenously every three weeks was started. The patient underwent five cycles of chemotherapy until
May 2015, continuing Denosumab and Leuprorelin. PSA decreased to 8.2 ng/mL, with limited clinical
benefit. After multidisciplinary evaluation, the patient was considered eligible for radiotherapy on
the prostatic region. This treatment was performed between May 2015 and July 2015 (total dose: 5400
cGy).

After radiation therapy, PSA raised to 17.4 ng/mL and the patient was referred to our department
for dorsal and abdominal pain. A total-body CT scan performed in August 2015 showed disease
progression, including rectal thickening, multiple liver metastasis, peritoneal carcinosis and increase
of abdominal and pelvic lymphadenomegalies. CT also showed disseminate osteoblastic metastasis
[Figure 3].