A 62-year-old man, with no significant past medical history, chronic smoker, and without known occupational exposure to carcinogens, presented with hematuria.

The patient reported macroscopic hematuria evolving for one month, with no associated symptoms. His general condition was preserved (ECOG 1).

Initial laboratory workup showed:

Hemoglobin: 11.2 g/dL.Creatinine: 11 mg/L.Creatinine clearance ≥ 60 mL/min.The lactate dehydrogenase (LDH) level was moderately elevated at 420 IU/L, corresponding to approximately 1.7 times the upper limit of normal.

Abdominopelvic CT scan revealed:

A 4-cm infiltrating bladder mass.Pelvic lymphadenopathy (up to 18 mm).Multiple bilobar liver metastases (up to 22 mm).Bone metastases.

The findings were consistent with de novo metastatic stage IV disease.

Cystoscopy showed a 4 - 5 cm exophytic bladder tumor. An incomplete transurethral resection of the bladder tumor (TURBT) was performed due to extensive tumor involvement and deep invasion of the bladder wall, which prevented safe complete resection.

Histology revealed:

Small round cells with scant cytoplasm and hyperchromatic nucleiNumerous mitotic figures and extensive necrosis

Immunohistochemistry was positive for:

SynaptophysinChromogranin ACD56, with a Ki-67 index of 80%

The diagnosis of small-cell neuroendocrine carcinoma of the bladder was confirmed.

Following multidisciplinary tumor board discussion, the patient received palliative platinum-based chemotherapy:

Cisplatin 75 mg/m² on Day 1.Etoposide 100 mg/m² on Days 1 – 3.

The regimen was repeated every 3 weeks.

The patient completed 6 cycles, well tolerated overall, except for grade 2 neutropenia managed with secondary prophylaxis using G-CSF.

After 3 cycles: Intermediate partial response with significant reduction of the bladder tumor and liver metastases.After 6 cycles: Sustained partial response, with disappearance of some liver lesions and persistence of small residual nodules.

Clinically, hematuria resolved and dysuria markedly improved.

However, within weeks after completing treatment, the patient’s general condition progressively deteriorated to ECOG 3, requiring exclusively palliative care. Second-line chemotherapy could not be initiated.

The patient died, with an overall survival of 8 months from diagnosis.

SCNEC of the bladder predominantly affects older men, with a mean age at diagnosis of about 67 years according to a clinical study of 51 patients [5]. Smoking is strongly associated with its development, reported in more than 50% of published cases [6].

Our patient (62 years old, heavy smoker) therefore fits the classical epidemiological profile.

Hematuria is the most common presenting symptom, observed in 67% - 100% of cases in the series by Grignon et al. [6].

Irritative or obstructive urinary symptoms may occur but are not constant. The frequent absence of systemic signs contributes to diagnostic delays [7].

The isolated macroscopic hematuria observed in our patient thus corresponds to the most typical clinical presentation.

SCNEC is characterized by early dissemination. In a study of 533 patients from the SEER registry, 35% already had metastatic disease at diagnosis, with a median survival of 12 months [8].

Liver metastases are among the most frequent sites, as also reported in a series of 15 metastatic patients from the Léon-Bérard Center [9].

The presence of liver metastases at diagnosis in our patient therefore aligns perfectly with this aggressive pattern.

Histologically, small hyperchromatic cells, numerous mitoses, and extensive necrosis are typical features of SCNEC. Immunohistochemistry confirms neuroendocrine differentiation through expression of synaptophysin, chromogranin A, and CD56 [5].

In an analysis of 81 cases, Wang et al. frequently reported Ki-67 > 70%, reflecting extreme tumor aggressiveness [10].

Our patient’s Ki-67 of 80% is consistent with these findings.

The differential diagnosis of small cell neuroendocrine carcinoma of the bladder includes high-grade urothelial carcinoma with neuroendocrine differentiation and metastatic small cell carcinoma from extra-vesical sites, particularly the lung. The predominance of neuroendocrine morphology, diffuse expression of neuroendocrine markers, and a high proliferation index support a diagnosis of primary small cell neuroendocrine carcinoma of the bladder. The absence of lung lesions on staging studies excludes a secondary origin.

The literature review has been updated to include recent data from systematic reviews and large database analyses published since 2018. These studies confirm the aggressive nature of SCNECB, with most patients diagnosed at an advanced or metastatic stage. Median overall survival remains very limited, often less than 12 months, despite an initial response to platinum-based chemotherapy. These data help contextualize our clinical observation within the current evidence and highlight the need for treatment strategies adapted to available resources.

In the absence of standardized guidelines, platinum-based chemotherapy (cisplatin or carboplatin) combined with etoposide is the most commonly used regimen, by analogy with small-cell lung carcinoma [11].

Initial response rates are often satisfactory, but relapses occur rapidly.

Our patient achieved a partial response after six cycles of cisplatin-etoposide, in line with results from published clinical series.

SCNEC carries a particularly poor prognosis. In a 20-year retrospective study of 38 patients, median survival was 11.8 months, with 1-, 3-, and 5-year survival rates of 47%, 26%, and 14% respectively [12].

In metastatic or relapsed patients, survival decreases to about 7 - 8 months despite chemotherapy [9].

The 8-month survival observed in our patient, along with rapid functional decline preventing second-line treatment, is therefore consistent with the expected disease course.

The rarity of SCNEC necessitates multicenter studies and the creation of international registries to better understand its mechanisms, optimize therapeutic strategies, and evaluate new potential treatments. Recent therapeutic advances, including immune checkpoint inhibitors, are currently under investigation in high-grade neuroendocrine carcinomas. Their role in the treatment of small cell neuroendocrine carcinoma of the bladder remains to be defined, and their availability is limited in many clinical settings.

In resource-limited countries, the management of small cell neuroendocrine carcinoma of the bladder is constrained by limited access to specialized immunohistochemistry, second-line treatments, and adequate supportive care.