Background: Chemotherapy using carboplatin and etoposide (CE) is frequently pragmatically proposed to treat metastatic prostate cancer (mPC), both primary small-cell neuroendocrine (PSC-NE) carcinoma and adenocarcinoma with or without neuroendocrine (NE) marker elevation. However, the real benefit of CE is poorly reported in the recent therapeutic context. Methods: We retrospectively analyzed the efficacy and tolerance of CE chemotherapy in these three different groups of mPC patients. Efficacy endpoints included radiological response, progression-free survival (PFS), and overall survival (OS), as well as PSA response and PFS2/PFS1 ratio in patients with adenocarcinoma. Results: Sixty-nine patients were included in this single-center study (N= 18 with PSC-NE carcinoma and 51 with adenocarcinoma with (N= 18) or without (N= 33) NE marker elevation). Patients with adenocarcinoma were highly pretreated with next-generation hormonal agents (NHAs) and taxanes. In patients with adenocarcinoma, a PSA response ≥50% was observed in six patients (15.8%), four of whom had NE marker elevation. The radiological response was higher in PSC-NE and tended to be higher in adenocarcinoma when NE marker elevation was present. Comparing patients with adenocarcinoma with vs. without NE marker elevation, the median PFS was 3.7 and 2.1 months and the median OS was 7.7 and 4.7 months, respectively. Overall, 62.3% of patients experienced grade 3–4 adverse events (mainly hematological), and three treatment-related deaths were recorded. Conclusion: Reports of the clinical results of CE suggest that we should not mix PSC-NE and castration-resistant adenocarcinoma of the prostate. In patients with heavily pretreated adenocarcinoma, the benefit/risk ratio of CE chemotherapy seems unfavorable due to poor response and high toxicity.
背景：卡铂联合依托泊苷（CE）化疗方案常被实际用于治疗转移性前列腺癌（mPC），包括原发性小细胞神经内分泌癌（PSC-NE）以及伴有或不伴有神经内分泌标志物升高的腺癌。然而，在当前治疗背景下，CE方案的实际获益情况尚缺乏充分报道。方法：本研究回顾性分析了CE化疗在以上三类不同mPC患者群体中的疗效与耐受性。疗效终点包括影像学缓解、无进展生存期（PFS）和总生存期（OS），以及腺癌患者的前列腺特异性抗原（PSA）缓解情况和PFS2/PFS1比值。结果：这项单中心研究共纳入69例患者（其中PSC-NE癌18例，伴有神经内分泌标志物升高的腺癌18例，不伴有神经内分泌标志物升高的腺癌33例）。腺癌患者绝大多数曾接受过新型内分泌药物和紫杉烷类药物的前期治疗。在腺癌患者中，6例（15.8%）观察到PSA下降≥50%，其中4例伴有神经内分泌标志物升高。PSC-NE癌患者的影像学缓解率更高，而伴有神经内分泌标志物升高的腺癌患者也呈现更高的缓解趋势。对比伴有与不伴有神经内分泌标志物升高的腺癌患者，中位PFS分别为3.7个月和2.1个月，中位OS分别为7.7个月和4.7个月。总体而言，62.3%的患者发生3-4级不良事件（主要为血液学毒性），并记录到3例治疗相关死亡。结论：CE方案的临床结果提示，不应将PSC-NE癌与去势抵抗性前列腺腺癌混为一谈。对于经过多重前期治疗的腺癌患者，CE化疗的获益风险比因疗效有限且毒性较高而显得不利。
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