Endocrine Oncology Unit, Gustave Roussy, F-94805, Villejuif, France.
Aix Marseille Université, INSERM, U1251, Department of Endocrinology, Marseille Medical Genetics (MMG), centre de référence des maladies rares de l'hypophyse (HYPO), hôpital de la Conception, France, Assistance Publique-Hôpitaux de Marseille (AP-HM), 13005 Marseille, France.
J Clin Endocrinol Metab. 2021 Aug 18;106(9):2726-2737. doi: 10.1210/clinem/dgab202.
The behavior of locally advanced pheochromocytoma (LAP) remains unknown.
We characterized the population with LAP and recurrence-free survival (RFS).
This retrospective multicentric study was run within the ENDOCAN-COMETE network and French Group of Endocrine Tumors (GTE) from 2003 to 2018, including patients from 11 French referral centers with LAP as defined by capsular invasion, vascular invasion, adipose tissue invasion, and/or positive locoregional lymph nodes at diagnosis without evidence of distant metastasis. The main outcome measure was recurrence, defined as tumor reappearance, including local site and/or distant metastasis. The primary endpoint was RFS analysis; secondary endpoints were characterization, overall survival (OS), and prognostic factors of recurrence.
Among 950 patients, 90 (9%) exhibited LAP criteria and 55 met inclusion criteria (median age, 53 years; 61% males; 14% with germline mutation; 84% with catecholamine excess). LAP was defined by 31 (56%) capsular invasions, 27 (49%) fat invasions, 6 (11%) positive lymph nodes, and 22 (40%) vascular invasions. After median follow-up of 54 months (range, 6-180), 12 patients (22%) had recurrences and 3 (5%) died of metastatic disease. Median RFS was 115 months (range, 6-168). Recurrences were local in 2 patients, distant in 2, and both local and distant in 8 patients. Median OS of patients was not reached. Size above 6.5 cm (P = 0.019) and Ki-67 > 2% (P = 0.028) were identified as independent significant prognostic factors in multivariate analysis.
LAP represents 9% of pheochromocytoma's population and has a metastatic behavior. This study paves the way for future pathological TNM classification.
局部晚期嗜铬细胞瘤（LAP）的行为尚不清楚。
我们对 LAP 患者的人群和无复发生存率（RFS）进行了特征描述。
这项回顾性多中心研究是在 2003 年至 2018 年期间在 ENDOCAN-COMETE 网络和法国内分泌肿瘤学组（GTE）内进行的，包括来自 11 个法国转诊中心的患者，这些患者被定义为 LAP，其诊断时具有包膜侵犯、血管侵犯、脂肪组织侵犯和/或阳性局部区域淋巴结，且无远处转移的证据。主要观察指标是复发，定义为肿瘤再现，包括局部部位和/或远处转移。主要终点是 RFS 分析；次要终点是特征描述、总生存（OS）和复发的预后因素。
在 950 例患者中，90 例（9%）表现出 LAP 标准，55 例符合纳入标准（中位年龄 53 岁；61%为男性；14%存在种系突变；84%存在儿茶酚胺过多）。LAP 通过 31 例（56%）包膜侵犯、27 例（49%）脂肪侵犯、6 例（11%）阳性淋巴结和 22 例（40%）血管侵犯来定义。在中位随访 54 个月（范围 6-180）后，12 例（22%）患者出现复发，3 例（5%）死于转移性疾病。中位 RFS 为 115 个月（范围 6-168）。2 例患者出现局部复发，2 例患者出现远处复发，8 例患者同时出现局部和远处复发。患者的中位 OS 未达到。多变量分析显示，肿瘤大小大于 6.5cm（P=0.019）和 Ki-67＞2%（P=0.028）是独立的显著预后因素。
LAP 占嗜铬细胞瘤人群的 9%，具有转移行为。这项研究为未来的病理 TNM 分类铺平了道路。
