前列腺黏液腺癌的临床特点与治疗策略：多中心36例经验总结

Clinical characteristics and treatment strategies of prostate mueinous adenocarcinoma： the multicenter summary of 36 cases

目的探讨前列腺黏液腺癌的临床特点及治疗策略。 方法回顾性分析2010年10月至2018年3月全国5家泌尿中心36例前列腺黏液腺癌患者的临床资料，其中上海长海医院9例，华中科技大学同济医学院附属同济医院4例，上海交通大学医学院附属仁济医院13例，南京医科大学第一附属医院8例，四川大学华西医院2例。年龄（66.8±7.2）岁（53～83岁）；中位PSA 22.89 ng/ml（2.67～1 786.00 ng/ml）。前列腺穿刺Gleason评分3＋3分6例，3＋4分9例，4＋3分5例，8分11例，9～10分5例。根据D’Amico危险分层，低危组2例，中危组9例，高危组25例。低危组2例和中危组9例均行根治手术。高危组25例中，22例器官局限性、局灶进展性及骨寡转移前列腺癌患者行根治手术；对于无法行根治术，伴有梗阻或血尿症状的3例转移性前列腺癌患者行姑息性前列腺电切或剜除术。2例根治术前行新辅助内分泌治疗。分析低、中、高危3组患者预后生存情况。 结果36例手术均顺利完成。25例根治术患者中23例行盆腔淋巴结清扫术，其中12例行双侧闭孔淋巴结清扫术，11例行双侧闭孔＋髂内＋髂外血管旁淋巴结清扫术。病理检查提示前列腺黏液腺癌9例，黏液腺癌伴腺泡腺癌26例，黏液腺癌伴神经内分泌化1例，其免疫组化染色检查示黏蛋白2（＋）。33例根治术后病理分期：≤T2b期12例（36.3%），T2c期7例（21.2%），T3a期7例（21.2%），T3b期6例（18.2%），T4期1例（3.0%）；盆腔淋巴结清扫阳性4例，切缘阳性9例。中位随访时间26个月（6～48个月），术后1年6例出现生化复发生，低危组0例，中危组3例，高危组3例。6例术后生化复发患者及22例根治术或姑息性电切术后PSA谷值〉0.2 ng/ml的患者行辅助全雄阻断治疗，术后辅助放化疗；4例进展为去势抵抗性前列腺癌（CRPC），均为高危组接受根治手术患者，进展至CRPC的中位时间26个月，其中2例死亡。另外，2例出现转移，其中1例根治术后5个月盆腔MRI检查示盆腔多发结节肿块，符合复发转移；另1例根治术后病理提示黏液腺癌神经内分泌化，术后3个月出现阴茎头转移。根治术后6、12个月尿控恢复率分别为86.2%（31/36）、88.9% （32/36）。 结论前列腺黏液腺癌是腺泡腺癌的一种亚型，其Gleason评分高，病理分期较晚，预后差异较大，易出现复发、转移。治疗策略上，中低危黏液腺癌建议根治手术治疗，预后较好，而高危黏液腺癌通过根治手术或姑息手术辅助全雄阻断综合治疗，大部分患者也可受益，少部分患者预后差。

ObjectiveTo review the clinical characteristics of prostate mucinous adenocarcinoma cases and update literatures , and recommend the corresponding clinical treatment strategy. MethodsFrom October 2010 to March 2018, 36 cases of prostate mucinous adenocarcinoma were involved from 5 urinary centers in China, including 9 cases from Shanghai Changhai Hospital, 4 cases from Wuhan Tongji Hospital, 13 cases from Shanghai Renji Hospitals, 8 cases from the First Affiliated Hospital of Nanjing Medical University, and 2 cases from Sichuan West China Hospitals. The patients′ age were （66.8±7.2） years （53-83 years） and the median PSA was 22.89 ng / ml （2.67-1786 ng / ml）. Prostate biopsy confirmed Gleason score 3＋ 3 points in 6 cases, 3＋ 4 points in 9 cases, 4＋ 3 points in 5 cases, 8 points in 11 cases, and 9 to 10 points in 5 cases. According to D′Amico risk stratification, 2 patients were in the low-risk group, 9 in the intermediate-risk group, and 25 in the high-risk group. Eight cases underwent radical retroperitoneal prostatectomy, 13 cases underwent laparoscopic radical prostatectomy, and 12 cases underwent robotic laparoscopic radical prostatectomy. Twenty-three cases underwent pelvic lymphadenectomy, including 12 cases of bilateral obturator lymph node dissection, and 11 cases of bilateral obturator＋ intraorbital＋ para-vascular para-aortic lymphadenectomy. ResultsAll 36 operations were completed successfully.Twenty-three cases underwent pelvic lymphadenectomy, including 12 of bilateral obturator lymph node dissection, and 11 of bilateral obturator, intraorbital, and para-aortic lymphadenectomy. Pathological examination showed 9 cases of prostate mucinous adenocarcinoma, 26 cases of mucinous adenocarcinoma with acinar adenocarcinoma, and 1 case of mucinous adenocarcinoma with neuroendocrine and immunohistochemical positive of MUC2（＋ ）. Among 33 cases undergoing radical surgery, the pathological stage of ≤T2b in 12 cases （36.3%）, T2c in 7 cases （21.2%）, T3a in 7 cases （21.2%）, T3b in 6 cases （18.2%）, and T4 in 1 case （3.0%）. Four cases had positive pelvic lymph nodes and 9 cases had positive margin. The median follow-up period was 26 months （6-48 months）. The biochemical recurrence occurred in 6 patients one year after surgery, including 3 cases in the intermediate-risk group and 3 cases in the high-risk group. Six cases with postoperative biochemical recurrence and 19 cases with PSA〉0.2 ng/ml after radical or palliative resection underwent adjuvant androgen deprivation therapy（ADT）, no postoperative adjuvant radiotherapy or chemotherapy was administered, and 4 cases progressed to castration-resistant prostate cancer. Four cases with CRPC were in the high-risk group and had underwent radical surgery, and the median period progressed to CRPC was 26 months（3-37months）with 2 cases of death. However, there was no significant difference in the rate of biochemical recurrence and the incidence of CRPC in the low-risk group, the intermediate-risk group and the high-risk group. In addition, 2 cases had metastases, with pelvic MRI presenting pelvic multiple nodular mass in one case which was consistent with recurrence and metastasis at the 5th month after radical surgery, and pathological examination presenting the mucinous adenocarcinoma being neurosecretory in another case and mestastasis being detected on glans at the 3rd months after radical surgery. The recovery rate of urinary continience at 6 and 12 months after radical surgery was 86.2%（31/36） and 89.7%（32/36） respectively. ConclusionsProstate mucinous adenocarcinoma is a variant of acinar adenocarcinoma. This study clarifies prostate mucinous adenocarcinoma of Chinese patients with high Gleason scores, advanced pathological stage, variant in prognosis, and prone to recurrence and metastasis. For treatment strategy, the low-risk and intermediate-risk mucinous adenocarcinoma is recommended undergoing radical surgery, and the prognosis maybe good. High-risk mucinous adenocarcinoma could treated with radical surgery or palliative surgery with adjuvant ADT, and most high-risk patients can benefite, with a small number of poor prognosis.