Cancer Res Treat.  2024 Apr;56(2):624-633. 10.4143/crt.2023.1076.

Clinical Outcomes of Small Cell Carcinoma of the Genitourinary Tract and the Prognostic Significance of the Tumor Immune Microenvironment

• Hyung J
• Kim HD
• Kim GH
• Cho YM
• Ryu YM
• Kim SY
• Park I
• Yoon S
• Lee JL

• KMID: 2554351
• DOI: http://doi.org/10.4143/crt.2023.1076

Abstract

Purpose
Small cell carcinoma of the genitourinary tract (GU SCC) is a rare disease with a poor prognosis. There are only limited treatment options due to insufficient understanding of the disease. In this study, we analyzed the clinical outcomes of patients with GU SCC and their association with the tumor immune phenotype.
Materials and Methods
Patients diagnosed with GU SCC were included. Survival outcomes according to the primary location (prostate and non-prostate) and stages (limited disease [LD] and extensive disease [ED]) were analyzed. We performed multiplex immunohistochemistry (IHC) in non-prostate SCC patients and analyzed the immune cell population.
Results
A total of 77 patients were included in this study. Their median age was 71 years, 67 patients (87.0%) were male, and 48 patients (62.3%) had non-prostate SCC. All patients with ED (n=31, 40.3%) received etoposide plus platinum (EP) as initial treatment and median overall survival (OS) was 9.7 months (95% confidence interval [CI], 7.1 to 18.6). Patients with LD (n=46, 59.7%) received EP followed by radiotherapy or surgery, and 24-months OS rate was 63.6% (95% CI, 49.9 to 81.0). The multiplex IHC analysis of 21 patients with non-prostate SCC showed that patients with a higher density of programmed death-ligand 1–expressing CD68+CD206+ M2-like macrophages had significantly worse OS outcomes with an adjusted hazards ratio of 4.17 (95% CI, 1.25 to 14.29; adjusted p=0.02).
Conclusion
Patients with GU SCC had a poor prognosis, even those with localized disease. The tumor immune phenotypes were significantly associated with survival. This finding provides new insights for treating GU SCC.

Keyword

Small cell carcinoma; Neuroendocrine carcinoma; Genitourinary tract; Multiplex immunohistochemistry

Figure

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  Fig. 1. Kaplan-Meier estimates of survival outcomes according to stage (limited disease [LD] vs. extensive disease [ED]) and primary tumor location (prostate vs. non-prostate genitourinary GU). Progression-free survival (PFS) (A) and overall survival (OS) (B) in both LD and ED. PFS (C) and OS (D) according to the primary tumor location in patients with LD. PFS (E) and OS (F) according to the primary tumor location in patients with ED. CI, confidence interval.

• 

  Fig. 2. Kaplan-Meier estimates of survival outcomes according to the local treatment modality (radiotherapy vs. surgery) following neoadjuvant etoposide plus platinum (EP) chemotherapy in patients with limited disease (n=46). (A) Progression-free survival (PFS). (B) Overall survival (OS). CCRT, concurrent chemoradiotherapy.

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  Fig. 3. (A, B) Representative slide images of multiplex immunohistochemistry. (C) Forest plot showing HRs of immune cell density and associations with OS analyzed by a Cox proportional hazards model. CI, confidence interval; DC, dendritic cell; HR, hazard ratio; OS, overall survival; PD-L1, programmed death-ligand 1. Kaplan-Meier estimates of OS according to immune cell density dichotomized at the median (D-F). (D) Programmed death-ligand 1 (PD-L1) expressing CD68+CD206+ M2-like macrophages. (E) PD-L1 expressing CD68+CD206– M1-like macrophages. (F) PD-L1 expressing cells.

Reference

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