原发性泌尿系小细胞癌的诊治与预后分析

Prognosis and treatment of primary urinary tract small cell carcinoma

目的 探讨泌尿系小细胞癌（urinary tract small cell carcinoma,UT-SCC）的临床病理特征、治疗方法及预后因素.方法 回顾性分析2000年6月至2014年12月收治的25例UT-SCC患者的临床资料,男22例,女3例.年龄45 ～ 79岁,平均67岁.膀胱小细胞癌20例,前列腺小细胞癌2例,肾盂、输尿管、腹膜后小细胞癌各1例.根据小细胞肺癌的分期系统将患者分为局限期和广泛期.膀胱小细胞癌20例中,局限期17例,广泛期3例;前列腺小细胞癌2例均为广泛期;肾盂、输尿管小细胞癌各1例均为局限期;腹膜后小细胞癌1例为广泛期.局限期膀胱小细胞癌17例中,行根治性膀胱切除术10例,术后6例行依托泊苷＋顺铂（EC）方案化疗,4例行吉西他滨＋顺铂（GC）方案化疗;拒绝根治性膀胱切除术7例,其中单纯行TURBT 2例,TURBT术后联合辅助化疗5例.2例前列腺小细胞癌行放疗联合化疗.2例上尿路小细胞癌（肾盂、输尿管）均行根治性肾输尿管全长切除＋膀胱袖状切除术.1例腹膜后小细胞癌留取活检后行肾穿刺造瘘术.分析患者的无进展生存期（progression-free survival,PFS）、总生存期（overall survival, OS）,分析TURBT术后是否联合辅助化疗及不同临床病理因素对PFS及OS的影响,采用Kaplan-Meier法绘制生存曲线并用Log-rank检验进行比较.结果 本组25例均经病理检查确诊为小细胞癌,根据病理结果分为14例单纯性UT-SCC和11例混合性UT-SCC.免疫组化染色检查：神经特异性烯醇化酶（neuron specific enolase,NSE）强阳性13例,弱阳性3例;嗜铬素A强阳性8例,弱阳性2例;NSE及嗜铬素A均为强阳性5例.UT-SCC局限期和广泛期患者的PFS分别为13.2个月和7.8个月,OS分别为27.2个月和12.7个月,差异均有统计学意义（χ2=13.53,P＜0.05;χ2=19.88,P＜0.05）.膀胱小细胞癌和泌尿系其他部位（肾盂、输尿管、前列腺、腹膜后）小细胞癌患者的PFS分别为12.8个月和8.2个月,OS分别为26.3个月和13.2个月,差异均有统计学意义（χ2 =12.00,P＜0.05;χ2=14.45,P＜0.05）.对根治性膀胱切除术后采用EC和GC方案化疗患者的PFS分别为16.3个月和12.5个月,OS分别为29.5个月和22.8个月,差异均无统计学意义（χ2 =3.34,P＞0.05;χ2 =1.66,P＞0.05）.膀胱小细胞癌单纯行TURBT术后行辅助化疗和未行辅助化疗对患者的PFS分别为14.5个月和12.0个月,OS分别为24.5个月和28.4个月,差异均无统计学意义（t=1.30,P＞0.05;t=0.50,P＞0.05）.结论 原发肿瘤的部位、肿瘤分期均对UT-SCC患者的预后产生影响,膀胱小细胞癌及局限期UT-SCC的生存期更长.

Objective To investigate the clinicopathological features, treatment modalities, and prognostic factors for survival in patients with urinary tract small cell carcinoma （UT-SCC）.Methods A total of 25 patients treated from June 2000 to December 2014 were included in the retrospective study.The data included age, gender, primary tumors origins, stage, treatment modalities, progression-free survival （PFS）, overall survival （OS）, pathology and immunohistochemistry.Of these cases, 22 were male, and the other was female, whose age was 45-79 years （mean age 67）.20 cases small cell carcinoma of bladder patients and 2 small cell carcinoma of prostate cancer patients were included.The number of small cell carcinoma in pelvis,ureter and retroperitoneal was 1 respectively.The patients with small cell carcinoma of the urinary tract were classified as disease and extensive disease.17 bladder small cell carcinomas were limited disease and 3 cases were extensive disease;Prostate small cell carcinomas were both extensive disease;The small cell carcinomas in pelvis, ureter were limited disease;The small cell carcinoma in retroperitoneal was extensive disease.10 bladder small cell carcinomas which were limited disease received radical cystectomy.6 of 10 patients received etoposide and cisplatnum （EC）.4 of 10 patients received gemcitabine and cisplatnum （GC）.7 bladder small cell carcinomas patients who with limited disease refused to receive radical cystectomy in which 2 patients received TURBT and 5 patients received TURBT followed chemotherapy.Both prostate small cell carcinomas received chemoradiotherapy.2 small cell carcinomas in upper urinary tract （pelvis and ureter） received radical nephroureterectomy with bladder cuff resection.The patient of retroperitoneal small cell carcinoma received percutaneous nephrostomy after biopsy.The progression-free survival （PFS） and overall survival （OS） of these patients are analyzed;the influence of TURBT with adjuvant chemotherapy and clinicopathologic characteristics were analyzed in median PFS and OS.PFS and OS were compared between groups as a function of time, using a Kaplan-Meier survival curve analysis and the log-rank significance test.All statistical tests were two-sided, and P values 〈 0.05 were considered statistically significant.Results 25 patients with a pathologic confirmation of UT-SCC,either by biopsy or surgery,were finally included.These patients were classified as pure UT-SCC （14） and Mixed UT-SCC （11）.Mixed UT-SCC was defined as tumors containing both SCC and non-SCC components,regardless of the proportion of the latter.13 cases were strongly positive and 3 cases were weakly positive in neuron specific enolase （NSE） level.8 cases were strongly positive and 2 cases were weakly positive in CgA level.Patients with limited disease experienced a significant longer PFS and OS compared with extensive disease subjects （PFS 13.2 vs.7.8 χ2=13.53 P〈0.01;OS27.2 vs.12.7χ2=19.88 P〈0.01）.Patients with bladder SCC showed a significantly higher median PFS and OS compared with patients with SCC of other parts of urinary tract （PFS 12.8 vs.8.2 χ2 =12.00, P =0.001;OS 26.3 vs.13.2 χ2 =14.45,P 〈0.01） .The two different chemotherapy regimens （GC and EC） have no influence on survival （PFS： 16.3 vs.12.5,χ2 =3.34, P =0.07;OS 29.5 vs.22.8, χ2 =1.66, P =0.198）.TURBT followed by adjuvant therapy have no influence on survival （PFS 14.5 vs.12.0 t =1.30 P =0.251;OS 24.5 vs.28.4 t =0.50,P =0.636）.Conclusions The primary tumors origins and stage may have influence on survival in patients with UT-SCC.Patients with bladder small cell carcinoma and limited disease experienced a longer survival.